Dimethyl Sulfate → HCID 86690090, compound
Reaction equation
[H-].[Na+].[F:3][C:4]1([F:17])[CH2:9][CH2:8][C:7]([CH2:15][OH:16])([C:10]([O:12][CH2:13][CH3:14])=[O:11])[CH2:6][CH2:5]1.S(OC)(O[CH3:22])(=O)=O>C1COCC1>[F:3][C:4]1([F:17])[CH2:5][CH2:6][C:7]([CH2:15][O:16][CH3:22])([C:10]([O:12][CH2:13][CH3:14])=[O:11])[CH2:8][CH2:9]1Participants
5
Reactant 3
Product 1
Reagents, catalysts & solvents 1
Procedure
NaH (60%, 29.4 mg, 0.736 mmol) was added to a cold (0° C.) solution of ethyl 4,4-difluoro-1-(hydroxymethyl)cyclohexanecarboxylate (109 mg, 0.490 mmol) in THF (2 mL) and the mixture was allowed to warm to rt over 30 min. Then neat dimethyl sulfate (0.070 mL, 0.736 mmol) was added and the mixture was stirred at rt overnight. Excess Me2SO4 was quenched with TEA, acidified with 1N HCl and extracted with EtOAc to afford a light brown oil which was purified by silica gel FCC (DCM) to afford ethyl 4,4-difluoro-1-(methoxymethyl)cyclohexanecarboxylate as a clear oil (47 mg). Ethyl ester was saponified as described for Cap-7 synthesis (1 N NaOH, MeOH-THF) to afford Cap-8 as a white solid: 1H NMR (400 MHz, CHLOROFORM-d) δ 3.47 (s, 2H), 3.39 (s, 3H), 2.25 (br. d, J=13.1 Hz, 2H), 2.10-1.95 (m, 3H), 1.69-1.55 (m, 3H).