Methyl chloroformate → 4-Fluoro-2-(1-methylcyclohexyl)phenyl methyl carbonate

HRID 1465150Notes

Reaction equation

HRID 1465150 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[C:4]([C:9]2([CH3:15])[CH2:14][CH2:13][CH2:12][CH2:11][CH2:10]2)[CH:3]=1.Cl[C:17]([O:19][CH3:20])=[O:18]>CN(C1C=CN=CC=1)C.ClCl>[C:17](=[O:18])([O:19][CH3:20])[O:8][C:5]1[CH:6]=[CH:7][C:2]([F:1])=[CH:3][C:4]=1[C:9]1([CH3:15])[CH2:14][CH2:13][CH2:12][CH2:11][CH2:10]1

Participants

5

Reactant 2

HCID 6586Methyl chloroformateHCID 593949974-Fluoro-2-(1-methylcyclohexyl)phenol

Product 1

HCID 593950614-Fluoro-2-(1-methylcyclohexyl)phenyl methyl carbonateYield 72.1%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 24526ChlorineSolvent

Procedure

To a solution of 4-fluoro-2-(1-methylcyclohexyl)phenol (23.5 g, 113 mmol), TEA (31 mL, 226 mmol) and DMAP (700 mg, 5.7 mmol) in CH2 Cl2(250 mL) was added methyl chloroformate dropwise at 0° C. The mixture was allowed to warm to room temperature and stirred for 2 hours. The reaction mixture was poured onto crushed ice and extracted with CH2Cl2(100 mL×3). The organic layer was washed with brine, dried over MgSO4, evaporated under vacuum. The crude product was purified by chromatography on silica gel diluted with (hexane:ethyl acetate=100:1) to give 4-fluoro-2-(1-methylcyclohexyl)phenyl methyl carbonate as red brown oil (43.9 g, 72.1% yield). 1H NMR (400 MHz, CDCl3) δ 7.10 (dd, J=3.2, 11.2 Hz, 1 H), 7.05-7.02 (m, 1H), 6.93-6.88 (m, 1H), 3.91 (s, 3H), 2.02-1.96 (m, 2H), 1.66-1.36 (m, 8H), 1.23 (s, 3H).

Workup

  1. additionThe reaction mixture was poured
  2. customonto crushed ice
  3. extractionextracted with CH2Cl2(100 mL×3)
  4. washThe organic layer was washed with brine
  5. dry with materialdried over MgSO4
  6. customevaporated under vacuum
  7. customThe crude product was purified by chromatography on silica gel
  8. additiondiluted with (hexane:ethyl acetate=100:1)

Sources & evidence

ORD record
ord-6e112277d32f4c7b92f5d6337442ef3f
Source dataset
uspto-grants-2015_04
Patent number
US08999976B2

Reaction notes

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