Methyl dichloroacetate → 2-Amino-5-(1-methyl-cyclopropyl)-thiazole-4-carboxylic acid methyl ester

HRID 1446685Notes

Reaction equation

[CH3:1][C:2]1([CH:5]=O)[CH2:4][CH2:3]1.[CH3:7][O:8][C:9](=[O:13])[CH:10](Cl)Cl.[Na].[NH2:15][C:16]([NH2:18])=[S:17]>C(OCC)C.CO>[CH3:7][O:8][C:9]([C:10]1[N:15]=[C:16]([NH2:18])[S:17][C:5]=1[C:2]1([CH3:1])[CH2:3][CH2:4]1)=[O:13]

Participants

Conditions

Temperature: 0 °C

Procedure

Combine 1-Methyl-cyclopropanecarbaldehyde (4.88 g, 58.01 mmol) and methyldichloroacetate (5.46 mL, 52.74 mmol) in diethyl ether (20 mL); cool to 0° C. Add dropwise a solution of sodium (1.21 g, 52.74 mmol) in methanol (20 mL). Stir the reaction mixture for 4 hours at 0° C. under N2. Extract the mixture with diethyl ether versus water. Dry the resulting organics over magnesium sulfate, filter, and concentrate to a clear liquid. Combine the liquid with thiourea (4.42 g, 58.01 mmol) in methanol (25 mL). Heat the reaction mixture for 14 hours at 60° C. under N2. Concentrate in vacuo and purify on a plug of silica gel, eluting with hexanes→3% methanol in dichloromethane→5% methanol in dichloromethane to afford product (5.10 g, 46% over two steps). MS (ES), m/z 213 (M+1).

Workup

extractionExtract the mixture with diethyl ether versus water
dry with materialDry the resulting organics over magnesium sulfate
filtrationfilter
concentrationconcentrate to a clear liquid
temperatureHeat the reaction mixture for 14 hours at 60° C. under N2
concentrationConcentrate in vacuo
custompurify on a plug of silica gel
washeluting with hexanes→3% methanol in dichloromethane→5% methanol in dichloromethane
customto afford product (5.10 g, 46% over two steps)

Sources & evidence

ORD record: ord-03f392b52ec34209a9e271dcbcb4aacf
Source dataset: uspto-grants-2010_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07666879B2

Reaction notes

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