Dimethyl Sulfate → Methyl 4,4-difluoro-1-methoxycyclohexanecarboxylate

HRID 520371Notes

Reaction equation

HRID 520371 reaction equation
[H-].[Na+].[F:3][C:4]1([F:14])[CH2:9][CH2:8][C:7](O)([C:10]([OH:12])=[O:11])[CH2:6][CH2:5]1.S([O:20][CH3:21])(OC)(=O)=O.[CH2:22]1COCC1>>[F:3][C:4]1([F:14])[CH2:9][CH2:8][C:7]([O:20][CH3:21])([C:10]([O:12][CH3:22])=[O:11])[CH2:6][CH2:5]1

Participants

5

Reactant 4

HCID 6497Dimethyl SulfateHCID 8028TetrahydrofuranHCID 24758Sodium hydrideHCID 401519704,4-Difluoro-1-hydroxycyclohexane-1-carboxylic acid

Product 1

HCID 86690092Methyl 4,4-difluoro-1-methoxycyclohexanecarboxylate

Procedure

NaH (60%, 2.2 equiv) was added to a cold (0° C.) stirred solution of 4,4-difluoro-1-hydroxycyclohexanecarboxylic acid (1 equiv) in THF (2 mL) and the mixture was allowed to warm rt (30 min). Then neat dimethyl sulfate (2.4 equiv) was added at 0° C. and the mixture was allowed to warm rt and stirred at rt overnight. Excess Me2SO4 was quenched with TEA and the reaction mixture was acidified with 1 N HCl, extracted with ether to afford methyl 4,4-difluoro-1-methoxycyclohexanecarboxylate which was saponified (1 N NaOH, THF-MeOH) to afford Cap-10 as a beige semi-solid. 1H NMR (400 MHz, CHLOROFORM-d) δ 3.36 (s, 3H), 2.17-1.98 (m, 8H).

Workup

  1. temperatureto warm rt
  2. customExcess Me2SO4 was quenched with TEA
  3. extractionextracted with ether

Sources & evidence

ORD record
ord-ce7ef91125074fc98496726405ed8857
Source dataset
uspto-grants-2016_05
Patent number
US09326973B2

Reaction notes

Loading…