Carbamate → tert-Butyl [2-(3-acetyl-5-chloro-2-ethoxy-6-fluorophenyl)-2-hydroxyethyl]carbamate

HRID 1499967Notes

Reaction equation

HRID 1499967 reaction equation
ClC1C=CC(C(O[NH:9][C:10](=[O:16])[O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=O)=CC=1.[Cl:19][C:20]1[C:21]([F:34])=[C:22]([CH:32]=[CH2:33])[C:23]([O:29][CH2:30][CH3:31])=[C:24]([C:26](=[O:28])[CH3:27])[CH:25]=1.C(=O)([O-:37])N>O.C(#N)C.[Os](=O)(=O)(=O)=O>[C:26]([C:24]1[C:23]([O:29][CH2:30][CH3:31])=[C:22]([CH:32]([OH:37])[CH2:33][NH:9][C:10](=[O:16])[O:11][C:12]([CH3:15])([CH3:14])[CH3:13])[C:21]([F:34])=[C:20]([Cl:19])[CH:25]=1)(=[O:28])[CH3:27]

Participants

7

Reactant 3

HCID 276CarbamateHCID 23655003tert-Butyl (4-Chlorobenzoyl)oxycarbamateHCID 866778781-(5-Chloro-2-ethoxy-4-fluoro-3-vinylphenyl)ethanone

Product 1

HCID 86677892tert-Butyl [2-(3-acetyl-5-chloro-2-ethoxy-6-fluorophenyl)-2-hydroxyethyl]carbamate

Reagents, catalysts & solvents 3

HCID 30318Osmium TetroxideCatalystHCID 962WaterSolvent2×HCID 6342AcetonitrileSolvent2×

Procedure

0.2 M Osmium tetraoxide in water (10 mL) was added to a solution of tert-butyl [(4-chlorobenzoyl)oxy]carbamate (Lawrence Harris, J. Org. Chem., 2011, 76, 358-372). (19 g, 70 mmol) in acetonitrile (210 mL) and stirred for 10 minutes. 1-(5-chloro-2-ethoxy-4-fluoro-3-vinylphenyl)ethanone (11.2 g, 46 mmol) (from Example 353, Step 1) as a solution in acetonitrile (210 mL) was added to the carbamate solution followed by the addition of water (50 mL) and the reaction was stirred for 3 hours at room temperature. The reaction was quenched with saturated 10 M dipotassium disulfite in water (240 mL) and stirred for 5 minutes. Water was added and the reaction mixture was extracted with ethyl acetate. The extracts were washed with saturated sodium bicarbonate solution, brine and dried over sodium sulfate, filtered and evaporated. Purification on silica gel using ethyl acetate in hexanes (0-100%) gave the desired compound as a racemic mixture, 16.6 g, 95%. LCMS calculated for C17H23ClFNO5Na (M+Na)+: m/z=398.1; found: 398.0.

Workup

  1. customThe reaction was quenched with saturated 10 M dipotassium disulfite in water (240 mL)
  2. stirringstirred for 5 minutes
  3. additionWater was added
  4. extractionthe reaction mixture was extracted with ethyl acetate
  5. washThe extracts were washed with saturated sodium bicarbonate solution, brine
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. customevaporated
  9. customPurification on silica gel

Sources & evidence

ORD record
ord-38932b9728104d3ab7b3993f0f472fe0
Source dataset
uspto-grants-2015_12
Patent number
US09199982B2

Reaction notes

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