All Notebooks | Help | Support | About
Templates
Risk Assessment
Archives
Authors
Sections
Yield
Reagent
Mnr
Aew
Ester Synthesis
  • 1 (1)
Tools
Show/Hide Keys
27th September 2012 @ 06:31
Reaction Scheme

Incomplete conversion of starting material after 27 hours reaction time. Trace amounts of product visible by UV, visualised by vanillin. Alternative method using sodium cyanoborohydride will be explored in AEW 9-2

PMY 2-5 (70 mg, 0.32 mmol, 1.1 equiv.) was stirred in anhydrous DCM (4.5 mL). 4-amino-1-benzylpiperidine (86 mg, 0.42 mmol, 1.3 equiv.) in DCM (1 mL) was added followed by freshly activated molecular sieves. The reaction mixture was stirred for 5 minutes at room temperature. Sodium triacetoxyborohydride (89 mg, 0.42 mmol, 1.3 equiv.) was added and the reaction left to stir at room temperature. After 2 hours, no conversion was observed by TLC. After 24 hours, still lots of starting material, one spot on the baseline (corresponding to the starting amine), not visible by UV, could be partially visualised with vanillin. Reaction not taken further Paul Ylioja suggested a method using sodium cyanoborohydride that had been effective in reductive amination of the same parent aldehyde See: Synthesis of amine-linked analogue of TCMDC-123812 via reductive amination using sodium cyanoborohydride in acidic conditions (PMY 38-5)

TLC (25% EtoAc in Hexane) visualised with UV and vanillin:
AEW 9-1.jpg

NB please ignore other TLC photo, this was uploaded in error

Risk and Hazard Assessment:
AEW 9-1 HIRAC.pdf


See also:
Synthesis of amine-linked analogue of TCMDC-123812 via reductive amination using sodium triacetoxyborohydride (PMY 38-2)

Reference:
doi:10.1021/jo960057x
Linked Entries
Attached Files
27th September 2012 @ 01:25
Reaction Scheme

TLC indicated some conversion to product but still large amounts of starting material. More promising than previous alkylations but suggests that esterification of AEW 3-3 is unfavourable. Isolation not attempted.

AEW 3-3 (120 mg, 0.55 mmol, 1 equiv.) was dissolved in anhydrous THF (5.0 mL) and cooled to 0 ˚C. NaH (26 mg, 0.66 mmol, 1.2 equiv) was added and then benzyl bromide (0.13 mL, 1.1 mmol, 2 equiv.) dissolved in anhydrous THF (0.5 mL) was added dropwise. Ice bath was removed and the reaction mixture was allowed to stir whilst reaching room temperature. TLC monitored over 6 hours and showed no conversion. After 24 hours 'product' visible on TLC (faint spot in UV, better visualised using vanillin).

Reaction abandoned, more promising than previous alkylations but slow conversion and decomposition products suggest that esterification is not favourable for this alcohol. See: Ester Synthesis (AEW 4-10) and linked posts.

TLC (25% EtoAc in hexane) after 24 hours, UV and vanillin:
AEW 8-1.jpg
AEW 8-1 vanillin.jpg


Hazard and Risk Assessment:
AEW 8-1 HIRAC.pdf
Linked Posts
This post is linked by:
Attached Files
25th September 2012 @ 06:16
Reaction Scheme

Pyrrole (1 g, 4.3 mmol, 1.0 equiv.) was dissolved in DMF (23 mL) at room temperature and then solid potassium carbonate (1.19 g, 6.0 mmol, 2 equiv.) added in two portions. Reaction mixture stirred at room temp. for 15 minutes and then 2-bromoacetamide (710 mg, 5.0 mmol, 1.2 equiv.) was added in a single portion and the reaction mixture stirred at room temperature for 1.5 hours. TLC analysis indicated product formation along with starting material.
Reaction mixture stirred for a further 1.5 h at room temperature.

TLC (100% EtOAc, stained with vanillin) after 1.5 h:
AEW 5-4 1.5 h.jpg
Linked Posts
This post is linked by:
Attached Files
24th September 2012 @ 08:03
AEW%204-10.png

A different batch of NaH was used and this time pre-stirred in THF as suggested by Anthony Lo

NaH (60% in mineral oil, 10 mg, 0.25 mmol, 1.1 equiv) was weighed into a flask, anhydrous THF (1 mL) was added and the suspension stirred stirred under Argon at 0 ˚C. AEW 3-2 (50 mg, 0.23 mmol, 1 equiv.) was dissolved in anhydrous THF (3 mL) and added drop wise at 0 ˚C. The reaction mixture was stirred at 0 ˚C for 10 minutes and then 2-bromoacetamide (32 mg, 0.23 mmol, 1 equiv.) was added in a single portion. The reaction mixture was allowed to stir whilst reaching room temperature for 3 hours. TLC showed SM and spot above (could be decomposition product seen in previous reactions). Reaction mixture allowed to stir at room temperature for a further 2 hours. TLC showed a greater amount of the upper spot. Left to stir at room temperature overnight.

TLC (25% EtOAc in Hexane) after 3 hours:
IMG_0048.jpg
Linked Posts
Attached Files
24th September 2012 @ 07:57
AEW%204-9.png

Potassium tert-butoxide (28 mg, 0.25 mmol, 1.1 eq) was weighed into a round-bottomed flask under Argon. 18-crown-6 (66 mg, 0.25 mmol, 1.1 equiv) dissolved in anhydrous THF (1 mL) was added and the reaction mixture was cooled to 0 ˚C. AEW 3-2 (50 mg, 0.23 mmol, 1 equiv.) was dissolved in anhydrous THF (3 mL) and added drop wise at 0 ˚C. The reaction mixture was stirred at 0 ˚C for 10 minutes and then 2-bromoacetamide (32 mg, 0.23 mmol, 1 equiv.) was added in a single portion. The reaction mixture was allowed to stir whilst reaching room temperature for 3 hours. TLC showed SM and spot above (could be decomposition product seen in previous reactions). Reaction mixture allowed to stir at room temperature for a further 2 hours. TLC showed a greater amount of the upper spot. Left to stir at room temperature overnight.

TLC (25% EtOAc in Hexane) after 3 hours:
IMG_0048.jpg
Linked Posts
This post is linked by:
Attached Files