Chlorodifluoromethane → HCID 57429434, compound

HRID 1640025Notes

Reaction equation

HRID 1640025 reaction equation
[OH:1][C:2]1[CH:3]=[CH:4][C:5]([CH3:13])=[C:6]([CH:12]=1)[C:7]([O:9][CH2:10][CH3:11])=[O:8].Cl[CH:15]([F:17])[F:16]>[OH-].[Na+].C(O)(C)C.ClCCl.O>[F:16][CH:15]([F:17])[O:1][C:2]1[CH:3]=[CH:4][C:5]([CH3:13])=[C:6]([CH:12]=1)[C:7]([O:9][CH2:10][CH3:11])=[O:8]

Participants

7

Reactant 2

HCID 6372ChlorodifluoromethaneHCID 15730468HCID 15730468, compound

Product 1

HCID 57429434HCID 57429434, compoundYield 59%

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 3776IsopropanolSolventHCID 6344DichloromethaneSolventHCID 14798Sodium HydroxideSolvent

Procedure

A mixture of ethyl 5-hydroxy-2-methylbenzoate (3.29 g, 18.2 mmol) in aqueous 30% sodium hydroxide (20 mL) and isopropyl alcohol (20 mL) was charged with 20 psi of chlorodifluoromethane in a high pressure flask, and stirred at room temperature for 10 min. After this time, the resulting mixture was heated at 50° C. for 0.5 h. After this time, the reaction mixture was cooled to room temperature and diluted with dichloromethane (50 mL) and water (200 mL). The organic layer was separated, dried over sodium sulfate, filtered, and concentrated under reduced pressure. Purification by flash chromatography (silica, gradient 0-7%, hexanes/ethyl acetate) afforded 2.50 g (59%) of ethyl 5-(difluoromethoxy)-2-methylbenzoate as colorless oil: 1H NMR (500 MHz, CDCl3) δ 7.67 (d, J=2.5 Hz, 1H), 7.26-7.22 (m, 1H), 7.18-7.16 (m, 1H), 6.50 (t, J=73.6 Hz, 1H), 4.37 (q, J=7.0 Hz, 2H), 2.57 (s, 3H), 1.40 (t, J=7.0 Hz, 3H); ESI MS m/z 231 [M+H]+.

Workup

  1. temperatureAfter this time, the resulting mixture was heated at 50° C. for 0.5 h
  2. temperatureAfter this time, the reaction mixture was cooled to room temperature
  3. customThe organic layer was separated
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customPurification by flash chromatography (silica, gradient 0-7%, hexanes/ethyl acetate)

Sources & evidence

ORD record
ord-e021b454dd62400a93d9397c8f664ba4
Source dataset
uspto-grants-2012_02
Patent number
US08110681B2

Reaction notes

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