Water → tert-butyl 4-(2,2-Difluoropropoxy)phenethylcarbamate

HRID 1749462Notes

Reaction equation

HRID 1749462 reaction equation
[OH:1][C:2]1[CH:17]=[CH:16][C:5]([CH2:6][CH2:7][NH:8][C:9](=[O:15])[O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[CH:4][CH:3]=1.CS(O[CH2:23][C:24]([F:27])([F:26])[CH3:25])(=O)=O.C(=O)([O-])[O-].[Cs+].[Cs+].O>CN(C=O)C>[F:26][C:24]([F:27])([CH3:25])[CH2:23][O:1][C:2]1[CH:17]=[CH:16][C:5]([CH2:6][CH2:7][NH:8][C:9](=[O:15])[O:10][C:11]([CH3:14])([CH3:12])[CH3:13])=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 962WaterHCID 10796Cesium carbonateHCID 11831452tert-butyl N-(2-(4-hydroxyphenyl)ethyl)carbamateHCID 873173442,2-Difluoropropyl methanesulfonate

Product 1

HCID 118162105tert-butyl 4-(2,2-Difluoropropoxy)phenethylcarbamateYield 14%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
115 °C

Procedure

A mixture of tert-butyl 4-hydroxyphenethylcarbamate (700 g, 2.94 mmol), 2,2-difluoropropyl methanesulfonate (668 mg, 3.84 mmol) and cesium carbonate (1.92 g, 5.88 mmol) in DMF (5 mL) was stirred at 115° C. in a microwave reactor for 3 h. After cooling to room temperature, water was added and extracted with ethyl acetate (3×100 mL). The combined organic layers were washed with brine, dried over anhydrous sodium sulfate and filtered. The filtrate was evaporated under vacuum to give the crude product, which was purified by preparative thin layer chromatography (22% ethyl acetate in petroleum ether) to afford the title compound (130 mg, 0.41 mmol, 14% yield). MS (ESI) m/z 316.1 [M+H]+.

Workup

  1. temperatureAfter cooling to room temperature
  2. extractionextracted with ethyl acetate (3×100 mL)
  3. washThe combined organic layers were washed with brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. customThe filtrate was evaporated under vacuum
  7. customto give the crude product, which
  8. customwas purified by preparative thin layer chromatography (22% ethyl acetate in petroleum ether)

Sources & evidence

ORD record
ord-487af577b35945f78ee71094ff8c7623
Source dataset
uspto-grants-2015_10
Patent number
US09156798B2

Reaction notes

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