Acetic Acid → (1S,2R)-2-(3-chlorophenyl)-1-(4-chlorophenyl)-N-(dicyclopropylmethyl)but-3-en-1-amine

HRID 932033Notes

Reaction equation

[Cl:1][C:2]1[CH:3]=[C:4]([C@@H:8]([CH:18]=[CH2:19])[C@@H:9]([C:11]2[CH:16]=[CH:15][C:14]([Cl:17])=[CH:13][CH:12]=2)[NH2:10])[CH:5]=[CH:6][CH:7]=1.[CH:20]1([C:23]([CH:25]2[CH2:27][CH2:26]2)=O)[CH2:22][CH2:21]1.C(O)(=O)C.C([BH3-])#N.[Na+]>CO.C(OCC)(=O)C>[Cl:1][C:2]1[CH:3]=[C:4]([C@@H:8]([CH:18]=[CH2:19])[C@@H:9]([C:11]2[CH:12]=[CH:13][C:14]([Cl:17])=[CH:15][CH:16]=2)[NH:10][CH:23]([CH:25]2[CH2:27][CH2:26]2)[CH:20]2[CH2:22][CH2:21]2)[CH:5]=[CH:6][CH:7]=1

Participants

Conditions

Temperature: 50 °C

Procedure

To a solution of 2.0 g (6.84 mmol) of (1S,2R)-2-(3-chlorophenyl)-1-(4-chlorophenyl)but-3-en-1-amine (Example 115, Step E), dicyclopropyl ketone (7.54 mL, 68.4 mmol), and acetic acid (1.96 mL, 34.2 mmol) in methanol (25.0 mL) was added sodium cyanoborohydride (1.44 mL, 27.4 mmol) at rt. The resulting mixture was stirred at 50° C. for 2 days. Acetic acid (1.5 ml) and sodium cyanoborohydride (0.6 g) were added again and heating was continued overnight. 200 ml of ethyl acetate was added, and the organic layer was washed consecutively with K2CO3 solution and sat. NaCl solution, dried over K2CO3, filtered and the filtrate was concentrated under reduced pressure at 60° C. The mixture was purified by flash chromatography on silica gel (eluent: DCM/MeOH, 95/5) to give the title compound.

Workup

temperatureheating
waitwas continued overnight
washthe organic layer was washed consecutively with K2CO3 solution and sat. NaCl solution
dry with materialdried over K2CO3
filtrationfiltered
concentrationthe filtrate was concentrated under reduced pressure at 60° C
customThe mixture was purified by flash chromatography on silica gel (eluent: DCM/MeOH, 95/5)

Sources & evidence

ORD record: ord-ee362d582942414d99f61cb8e7683373
Source dataset: uspto-grants-2016_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09296736B2

Reaction notes

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