Sodium Hydroxide → 1-(Tert-butoxycarbonylamino)-2-(difluoromethyl)cyclopropanecarboxylic acid
Reaction equation
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]Participants
Reactant 3
Product 1
Reagents, catalysts & solvents 1
Procedure
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.
Workup
- concentrationThe reaction mixture was concentrated
- customA white solid precipitated from the solution
- customwas collected by filteration
- washThe filter cake was washed with water
- customto yield 1.2 g of the crude product as a white solid
- customCrystallization from hexane/EtOAc
Sources & evidence
- ORD record
- ord-0d036ed8ecab4a14a48ec2a4d0714625
- Source dataset
- uspto-grants-2011_02
- Patent number
- US07888464B2
Reaction notes
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