Chloroacetaldehyde → (trans)-N-(2-chloroethyl)-2-(3'-(trifluoromethyl)biphenyl-4-yl)cyclopropanamine
Reaction equation
[F:1][C:2]([F:20])([F:19])[C:3]1[CH:4]=[C:5]([C:9]2[CH:14]=[CH:13][C:12]([C@@H:15]3[CH2:17][C@H:16]3[NH2:18])=[CH:11][CH:10]=2)[CH:6]=[CH:7][CH:8]=1.[Cl:21][CH2:22][CH:23]=O>C(Cl)Cl>[Cl:21][CH2:22][CH2:23][NH:18][C@@H:16]1[CH2:17][C@H:15]1[C:12]1[CH:13]=[CH:14][C:9]([C:5]2[CH:6]=[CH:7][CH:8]=[C:3]([C:2]([F:19])([F:20])[F:1])[CH:4]=2)=[CH:10][CH:11]=1Participants
Procedure
To a solution of (trans)-2-(3′-(trifluoromethyl)biphenyl-4-yl)cyclopropanamine (3.6 g, 38.26 mmol) in DCM (36 mL), 4° A molecular sieves was added followed by chloroacetaldehyde (5.8 mL, 38.26 mmol) and then stirred at RT for 1 h. After completion, monitored by TLC, cooled the reaction mixture at −10° C. and Na(CN)BH3 (2.88 g, 45.92 mmol) was added and stirred at RT for 2 h. After completion, the reaction mixture was quenched with NH4Cl (5%) and filtered through a pad of celite. The filtrate was extracted with DCM (2×50 mL), combined extracts were washed with water (40 mL), dried over anhydrous Na2SO4, filtered and evaporated. The residue was purified by flash column chromatography by using EtOAc: Pet ether to get (trans)-N-(2-chloroethyl)-2-(3′-(trifluoromethyl)biphenyl-4-yl)cyclopropanamine (3.2 g, 72.72%) as a liquid.
Workup
- temperaturecooled the reaction mixture at −10° C.
- stirringstirred at RT for 2 h
- customAfter completion, the reaction mixture was quenched with NH4Cl (5%)
- filtrationfiltered through a pad of celite
- extractionThe filtrate was extracted with DCM (2×50 mL)
- washwere washed with water (40 mL)
- dry with materialdried over anhydrous Na2SO4
- filtrationfiltered
- customevaporated
- customThe residue was purified by flash column chromatography
Sources & evidence
- ORD record
- ord-f805dc976dbf40718e2982b836207687
- Source dataset
- uspto-grants-2014_10
- Patent number
- US08859555B2
Reaction notes
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