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26th March 2013 @ 18:12

 

The title compound was synthesised according to the procedure of Carrol[1] with no modifications. 

References:

 1) 5‐Amino‐2H‐pyran‐3(6H)‐one, 1, a Convenient Intermediate in the Synthesis of Pyran Containing 1,4‐Dihydropyridines DOI:10.1081/SCC-120027702

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26th March 2013 @ 15:13

 

PT-1-11A (16.6 mg 48.8 umol), was suspended in MeOH (10 ml) and saturated aqueous ammonia (10 ml) and stirred for 30 minutes, whereupon TLC indicated completion. The reaction was concentrated in vacuo to give a solid which was purified the same way as Amidation of PT-1-9A (PT-1-10) then dried in vacuo to give a white solid PT-1-12-C1 (7 mg, 21 umol, 43%, Rf 0.55 (ethyl acetate)). 

 

Analysis: NMR consistent with Amidation of PT-1-9A (PT-1-10), sans N-methyl group and introduction of an N-H at 5.1 ppm, plus traces of ethyl acetate. Mass spec consistent (ESI-Nom).

ESI-Acc (Finnegan MAT-900 ESI-Positive HRMS): Expected 325.08909 (C14H16O3N3FS) Found 325.08881 (0.28 ppm)

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8th March 2013 @ 10:57

 

Following the procedure of Amination of PT-1-4 (PT-1-9), crude product Resynthesis of MD 6-3 (PT-1-4) (120 mg, 62% purity, 0.2 mmol) was suspended in 1ml of dry dichloromethane and to this was added dry dimethylformamide (1 equivalent, 14 mg, 15 ul, ca. 1 drop) followed by dropwise oxalyl chloride (8 equivalents, 203 mg, 137 uL). The reaction mixture was stirred at room temperature under an atmosphere of dry nitrogen overnight, whereupon TLC indicated generation of the acid chloride. The reaction mixture was diluted with dichloromethane (25 ml) and washed with water (25 ml), then dried over MgSO4 and concentrated in vacuo to give a brown oil (ca. 130 mg). This oil was suspended in dry pyridine (10 ml) and to this was added glycine methyl ester hydrochloride (5 eq, 1 mmol, 126 mg). The reaction mixture was stirred at room temperature for three hours, whereupon TLC indicated consumption of the acid chloride (Rf = 0.6, 1:1 ethyl acetate:heptane, PT-1-11-A1 TLC, left-hand spot) with concommitant appearance of a new product (Rf = 0.3, 1:1 ethyl acetate:heptane, PT-1-11-A1 TLC, right-hand spot). The solvents were removed in vacuo and the residue purified by DCVC (gradient, ethyl acetate/heptane, 25, 33, 41, 50, 66, 83, 100%) to givea tan oil (16.6 mg, 48 umol, 24%)

 Risk Assessment as in Amination of PT-1-4 (PT-1-9)

Analysis:

PT-1-11-C1 13C.pdf
PT-1-11-C1 1H.pdf

1H and 13C were consistent with desired product plus some solvent residual peaks. By analogy to the N-methyl analogue previously prepared Resynthesis of MD 6-3 (PT-1-4), the CH3 peak at 2.9 ppm is no longer present. 

 

Additional Observations: crude samples decomposed in NMR tubes at room temperature with indirect sunlight over the course of 72 hours. Reduced yield due to the second step not going to completion; TLC indicated absence of SM but may have been present as the activated ester pyridinium complex.

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1st March 2013 @ 10:23

 

The product from the previous step Amination of PT-1-4 (PT-1-9) (42.1 mg 118 umol), was suspended in MeOH (10 ml) and saturated aqueous ammonia (10 ml) and stirred for 1 hour, whereupon TLC (PT-1-10-A1) indicated completion (ca. 90% pure by NMR, PT-1-10-B1). The reaction was concentrated in vacuo and purified by dry column vacuum chromatogrphy (gradient: 50-100% ethyl acetate, background heptane, 6 fractions, then ethyl acetate, 6 fractions) to give the desired product as a white foam (28.1 mg, 82 umol, 69%).

 

Analysis:

PT-1-10-C1 MS nominal.jpg
PT-1-10-C1 NMR 1H.pdf
PT-1-10-C1 NMR 13C.pdf






Mass spectroscopy: ESI-NOM found 362.0 [M+Na]+, 700.6 [2M + Na]+.

ESI-Acc (Finnegan MAT-900 ESI-Positive HRMS): Expected 339.10474 (C15H18O3N3FS) Found 339.10460 (0.14 ppm)

 

NMR Spectroscopy: Consistent with expected product.

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