Dimethyl Sulfate → HCID 86690090, compound

HRID 520369Notes

Reaction equation

HRID 520369 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]1

Participants

5

Reactant 3

HCID 6497Dimethyl SulfateHCID 24758Sodium hydrideHCID 58815088HCID 58815088, compound

Product 1

HCID 86690090HCID 86690090, compoundYield 40.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

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).

Workup

  1. customExcess Me2SO4 was quenched with TEA
  2. extractionextracted with EtOAc
  3. customto afford a light brown oil which
  4. customwas purified by silica gel FCC (DCM)

Sources & evidence

ORD record
ord-6af963e19a3945178c5cd93d68d0d6b9
Source dataset
uspto-grants-2016_05
Patent number
US09326973B2

Reaction notes

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