Ethyl Acetate → HCID 67584325, compound

HRID 1456551Notes

Reaction equation

HRID 1456551 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[C:4]([CH2:9][CH2:10][C:11]2[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=2)[CH:3]=1.CC(C)([O-])C.[K+].Cl[CH2:25][CH2:26][C@@H:27]1[CH2:31][C@@H:30]([O:32][Si](C(C)(C)C)(C)C)[CH2:29][N:28]1[C:40]([O:42][C:43]([CH3:46])([CH3:45])[CH3:44])=[O:41].C(OCC)(=O)C>CN(C)C(=O)C>[C:43]([O:42][C:40]([N:28]1[CH2:29][C@H:30]([OH:32])[CH2:31][C@H:27]1[CH2:26][CH2:25][O:8][C:5]1[CH:6]=[CH:7][C:2]([F:1])=[CH:3][C:4]=1[CH2:9][CH2:10][C:11]1[CH:12]=[CH:13][C:14]([F:17])=[CH:15][CH:16]=1)=[O:41])([CH3:46])([CH3:45])[CH3:44]

Participants

6

Reactant 4

HCID 8857Ethyl AcetateHCID 22106952HCID 22106952, compoundHCID 23665647Potassium tert-butoxide2×HCID 57301849HCID 57301849, compound

Product 1

HCID 67584325HCID 67584325, compoundYield 74%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Procedure

687 mg of 4-fluoro-2-[2-(4-fluorophenyl)ethyl]phenol (prepared as described in Preparation 6) were dissolved in 12 ml of N,N-dimethylacetamide, and then 212 mg of potassium t-butoxide were added to the resulting solution, whilst ice-cooling. The resulting mixture was then stirred for 10 minutes, after which 687 mg of (2S,4R)-2-(2-chloroethyl)-1-t-butoxycarbonyl-4-t-butyldimethylsilyloxypyrrolidine were added. The resulting mixture was then stirred at room temperature for 14 hours. At the end of this time, 135 mg of potassium t-butoxide were added to the reaction mixture, and the mixture was stirred at 40° C. for 4 hours, after which 300 ml of ethyl acetate were added. The resulting reaction mixture was washed with water and with a saturated aqueous solution of sodium chloride, in that order. The ethyl acetate layer was separated and dried over anhydrous magnesium sulfate. It was then concentrated by evaporation under reduced pressure. The resulting oily substance was purified by silica gel column chromatography, using a 2:3 by volume mixture of hexane and ethyl acetate as the eluent, to give 571 mg (yield 74%) of the title compound as a colorless oily substance.

Workup

  1. temperaturecooling
  2. stirringThe resulting mixture was then stirred at room temperature for 14 hours
  3. stirringthe mixture was stirred at 40° C. for 4 hours
  4. customThe resulting reaction mixture
  5. washwas washed with water and with a saturated aqueous solution of sodium chloride, in that order
  6. customThe ethyl acetate layer was separated
  7. dry with materialdried over anhydrous magnesium sulfate
  8. concentrationIt was then concentrated by evaporation under reduced pressure
  9. customThe resulting oily substance was purified by silica gel column chromatography
  10. additionby volume mixture of hexane and ethyl acetate as the eluent

Sources & evidence

ORD record
ord-9b3e34053f2142b590ce0b374d842f97
Source dataset
uspto-grants-1998_12
Patent number
US05843983

Reaction notes

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