Ethyl chloroformate → HCID 58293818, compound

HRID 446722Notes

Reaction equation

HRID 446722 reaction equation
[S:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[CH2:6][NH:7][CH2:8][CH2:9][C:10]([O:12][CH3:13])=[O:11].O.C1COCC1.C(=O)(O)[O-].[Na+].Cl[C:26]([O:28][CH2:29][CH3:30])=[O:27]>O>[CH2:29]([O:28][C:26]([N:7]([CH2:6][C:2]1[S:1][CH:5]=[CH:4][CH:3]=1)[CH2:8][CH2:9][C:10]([O:12][CH3:13])=[O:11])=[O:27])[CH3:30]

Participants

6

Reactant 4

HCID 10928Ethyl chloroformateHCID 516892Sodium BicarbonateHCID 21881883Oxolane--water (1/1)HCID 23369385HCID 23369385, compound

Product 1

HCID 58293818HCID 58293818, compound

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

To a solution of Compound 1040 (35.2 g, 176.6 mmol) in 1:1 water/THF (1. L) was added solid sodium bicarbonate (32.6 g, 388.6 mmol) and ethyl chloroformate (20.3 mL, 212.0 mmol). The reaction was stirred at room temperature overnight, at which point LCMS indicated complete disappearance of starting material. The reaction mixture was diluted with water, extracted with ethyl acetate, and the volatiles removed under reduced pressure to give methyl 3-(ethoxycarbonyl(thiophen-2-ylmethyl)amino)propanoate as a pale yellow oil (Compound 1041, 19.9 g, 41%); 1H NMR (300 MHz, CDCl3): δ 7.20-7.12 (m, 1H), 6.94-6.83 (m, 2H), 4.56 (s, 2H), 4.10 (td, J=14.5, 7.3 Hz, 2H), 3.52 (s, 3H), 3.46 (t, J=6.6 Hz, 2H), 2.47-2.39 (m, 2H), 1.97 (s, H) and 1.24-1.15 (m, 3H) ppm. The aqueous layer contained some 3-(ethoxycarbonyl(thiophen-2-ylmethyl)amino)propanoic acid (Compound 1042) resulting from hydrolysis of the methyl ester. Compound 1042 could be isolated by adjusting the pH of the aqueous layer to 2 with 6M HCl followed by extraction with 10% n-BuOH in chloroform, which after concentration gave the carboxylic acid as a pale yellow oil (17.33 g).

Workup

  1. extractionextracted with ethyl acetate
  2. customthe volatiles removed under reduced pressure

Sources & evidence

ORD record
ord-d23bb71862474c5bb9a9303cc4d49f5c
Source dataset
uspto-grants-2013_07
Patent number
US08481524B2

Reaction notes

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