Chloroacetyl chloride → (1S)-1-(4-fluorophenyl)-2-(N-benzyl-N-chloroacetylamino)ethanol

HRID 880229Notes

Reaction equation

[CH2:1]([NH:8][CH2:9][C@H:10]([C:12]1[CH:17]=[CH:16][C:15]([F:18])=[CH:14][CH:13]=1)[OH:11])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[OH-].[Na+].[Cl:21][CH2:22][C:23](Cl)=[O:24]>C(Cl)Cl>[CH2:1]([N:8]([CH2:9][C@H:10]([C:12]1[CH:13]=[CH:14][C:15]([F:18])=[CH:16][CH:17]=1)[OH:11])[C:23](=[O:24])[CH2:22][Cl:21])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

Conditions

Temperature: 0 °C

Procedure

Dissolve (1S)-2-(benzylamino)-1-(4-fluorophenyl)ethanol (1215 g, 4.96 mol) in 12.15 L DCM and cool the mixture to 0° C. Add NaOH (1M in H2O, 5.46 L, 5.46 mol) dropwise over 30 min. Stir the mixture vigorously for 10 min while maintaining it at 0-3° C.; then add a solution of chloroacetyl chloride (616.5 g, 5.46 mol) in 4.86 L of DCM dropwise over 1 h keeping the temperature below 6° C. Stir the mixture for 1 h at 0° C.; separate the layers; and extract the aqueous phase with DCM (1×2 L). Combine the organic layer and extracts; wash them with 10% hydrochloric acid (1.5 L), water (1.5 L) and 1M NaOH (1 L). Dry over Na2SO4 and filter. Collect the filtrate and remove the solvent under reduced pressure to provide the title compound as a colorless oil (1440 g, 90%). MS (m/z): 322 (M+1).

Workup

temperaturewhile maintaining it at 0-3° C.
customthe temperature below 6° C
stirringStir the mixture for 1 h at 0° C.
customseparate the layers
extractionand extract the aqueous phase with DCM (1×2 L)
washwash them with 10% hydrochloric acid (1.5 L), water (1.5 L) and 1M NaOH (1 L)
dry with materialDry over Na2SO4
filtrationfilter
customCollect the filtrate
customremove the solvent under reduced pressure

Sources & evidence

ORD record: ord-87c36800012b4a70928596776248f882
Source dataset: uspto-grants-2015_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08993568B2

Reaction notes

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