4-Methylmorpholine → Methyl 3-methyl-2-(4-(4-nitrophenyl)thiazole-2-carboxamido)butanoate

HRID 1024433Notes

Reaction equation

CN1CCOCC1.[N+:8]([C:11]1[CH:16]=[CH:15][C:14]([C:17]2[N:18]=[C:19]([C:22]([O:24]CC)=O)[S:20][CH:21]=2)=[CH:13][CH:12]=1)([O-:10])=[O:9].ClC(OCC(C)C)=O.Cl.[CH3:36][O:37][C:38](=[O:44])[C@H:39]([CH:41]([CH3:43])[CH3:42])[NH2:40]>C1COCC1.C(N(CC)CC)C>[CH3:42][CH:41]([CH3:43])[CH:39]([NH:40][C:22]([C:19]1[S:20][CH:21]=[C:17]([C:14]2[CH:13]=[CH:12][C:11]([N+:8]([O-:10])=[O:9])=[CH:16][CH:15]=2)[N:18]=1)=[O:24])[C:38]([O:37][CH3:36])=[O:44]

Participants

Conditions

Temperature: -20 °C

Procedure

N-methyl morpholine (1.8 gm) was added to a solution of 4-(4-nitrophenyl)thiazole-2-carboxylic acid (Intermediate 3, step B, 4.5 gm) in THF (300 ml). The reaction mixture was stirred for 5 minutes and then cooled to −20° C. Isobutyl chloroformate (2.45 gm) was added to it and the reaction mixture was stirred for 20 minutes. To it was added L-valine methyl ester hydrochloride (7.2 gm) previously neutralized with triethylamine (4.63 gm) and the reaction mass was stirred for 3 hours as the temperature rose to RT. Organic solvent was concentrated and compound was purified by column chromatography (silica gel, EtOAc-petroleum ether) to obtain yellow solid as title compound. Yield: 4.4 gm (67%). 1H NMR (DMSO-d6, 300 MHz): δ 8.36 (d, 2H), 8.14 (d, 2H), 7.94 (s, 1H), 7.80 (d, 1H), 4.77 (t, 1H), 3.83 (s, 3H), 2.37 (m, 1H), 1.071 (s, 6H).

Workup

stirringthe reaction mixture was stirred for 20 minutes
stirringthe reaction mass was stirred for 3 hours as the temperature
customrose to RT
concentrationOrganic solvent was concentrated
customcompound was purified by column chromatography (silica gel, EtOAc-petroleum ether)

Sources & evidence

ORD record: ord-9dd400d12863404fb7187b9361e0b316
Source dataset: uspto-grants-2014_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08722901B2

Reaction notes

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