Chloroacetyl chloride → HCID 66975041, compound

HRID 1022561Notes

Reaction equation

HRID 1022561 reaction equation
[CH2:1]([NH:8][CH2:9][CH:10]([CH2:21][O:22][Si:23]([C:26]([CH3:29])([CH3:28])[CH3:27])([CH3:25])[CH3:24])[CH:11]([C:13]1[CH:18]=[CH:17][C:16]([F:19])=[C:15]([Cl:20])[CH:14]=1)[OH:12])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(N(CC)CC)C.Cl[CH2:38][C:39](Cl)=[O:40]>C1COCC1>[CH2:1]([N:8]1[CH2:9][CH:10]([CH2:21][O:22][Si:23]([C:26]([CH3:29])([CH3:28])[CH3:27])([CH3:25])[CH3:24])[CH:11]([C:13]2[CH:18]=[CH:17][C:16]([F:19])=[C:15]([Cl:20])[CH:14]=2)[O:12][CH2:38][C:39]1=[O:40])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 6577Chloroacetyl chlorideHCID 8471TriethylamineHCID 66975486HCID 66975486, compound

Product 1

HCID 66975041HCID 66975041, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of (1RS,2SR)-3-(benzylamino)-2-({[tert-butyl(dimethyl)silyl]oxy}methyl)-1-(3-chloro-4-fluorophenyl)propan-1-ol (14.1 g) and triethylamine (4.95 mL) in THF (100 mL) was added chloroacetyl chloride (2.59 ml) under ice-cooling, and the mixture was stirred at 0° C. for 18 hr. The reaction mixture was concentrated under reduced pressure, and the residue was diluted with ethyl acetate. The diluted solution was washed with distilled water and brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The obtained mixture was diluted with THF (300 ml), 1 N aqueous sodium hydroxide solution (63 mL) was added dropwise under ice-cooling, and the mixture was stirred at room temperature for 2 hr. The reaction mixture was concentrated under reduced pressure, and the residue was diluted with ethyl acetate. The diluted solution was washed with distilled water, saturated aqueous sodium hydrogen carbonate and brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel chromatography (hexane/ethyl acetate) to give the title compound (6.72 g).

Workup

  1. temperaturecooling
  2. concentrationThe reaction mixture was concentrated under reduced pressure
  3. additionthe residue was diluted with ethyl acetate
  4. washThe diluted solution was washed with distilled water and brine
  5. dry with materialdried over anhydrous magnesium sulfate
  6. concentrationconcentrated under reduced pressure
  7. additionThe obtained mixture was diluted with THF (300 ml), 1 N aqueous sodium hydroxide solution (63 mL)
  8. additionwas added dropwise under ice-
  9. temperaturecooling
  10. stirringthe mixture was stirred at room temperature for 2 hr
  11. concentrationThe reaction mixture was concentrated under reduced pressure
  12. additionthe residue was diluted with ethyl acetate
  13. washThe diluted solution was washed with distilled water, saturated aqueous sodium hydrogen carbonate and brine
  14. dry with materialdried over anhydrous magnesium sulfate
  15. concentrationconcentrated under reduced pressure
  16. customThe residue was purified by silica gel chromatography (hexane/ethyl acetate)

Sources & evidence

ORD record
ord-9968ac3e5b4343678b3b1096629423ee
Source dataset
uspto-grants-2014_05
Patent number
US08722662B2

Reaction notes

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