C(OC([N:11]([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[C:12]1([C:18]([O:20]C)=[O:19])[CH2:14][CH:13]1[CH:15]([F:17])[F:16])=O)C1C=CC=CC=1.C(OC(NC1(C(OC)=O)CC1C(F)F)=O)(C)(C)C.[OH-].[Na+]>CO>[C:25]([O:24][C:22]([NH:11][C:12]1([C:18]([OH:20])=[O:19])[CH2:14][CH:13]1[CH:15]([F:17])[F:16])=[O:23])([CH3:28])([CH3:26])[CH3:27]
A mixture of methyl 1-((benzyloxycarbonyl)(tert-butoxycarbonyl)amino)-2-(difluoromethyl)cyclopropanecarboxylate (1.05 g, 2.63 mmol), methyl 1-(tert-butoxycarbonylamino)-2-(difluoromethyl)cyclopropanecarboxylate (1.43 g, 5.39 mmol) in MeOH (20 mL) and sodium hydroxide (10 mL, 40.0 mmol) was stirred at rt for 18 h. The reaction mixture was concentrated and adjusted to pH=4 using 1N HCl. A white solid precipitated from the solution and was collected by filteration. The filter cake was washed with water to yield 1.2 g of the crude product as a white solid. Crystallization from hexane/EtOAc gave 1.0 g (50%) of 1-(tert-butoxycarbonylamino)-2-(difluoromethyl)cyclopropanecarboxylic acid as a white solid. This intermediate was isolated as a single diastereoisomer wherein the CF2H substituent is syn to the carboxyl group.
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