Triethylamine → [4-(2-chloroethyl)phenyl]-[(2S)-2-(pyrrolidin-1-ylmethyl)pyrrolidin-1-yl]methanone

HRID 1676948Notes

Reaction equation

[Cl:1][CH2:2][CH2:3][C:4]1[CH:12]=[CH:11][C:7]([C:8]([OH:10])=O)=[CH:6][CH:5]=1.C(N(CC)CC)C.[NH:20]1[CH2:24][CH2:23][CH2:22][C@H:21]1[CH2:25][N:26]1[CH2:30][CH2:29][CH2:28][CH2:27]1>S(Cl)(Cl)=O.ClCCl>[Cl:1][CH2:2][CH2:3][C:4]1[CH:5]=[CH:6][C:7]([C:8]([N:20]2[CH2:24][CH2:23][CH2:22][C@H:21]2[CH2:25][N:26]2[CH2:30][CH2:29][CH2:28][CH2:27]2)=[O:10])=[CH:11][CH:12]=1

Participants

Conditions

Temperature: 50 °C

Procedure

4-(2-Chloroethyl)benzoic acid (1.00 g, 5.4 mmol) is dissolved in thionyl chloride (6.0 mL) and stirred at 50° C. for 30 min. The excess thionyl chloride is removed in vacuo and the residue is dissolved in dichloromethane (2 mL) to make a solution of the acid chloride. Triethylamine (656 mg, 6.5 mmol) and (S)(+)-1-(2-pyrrolidinylmethyl)pyrrolidine (1.00 g, 6.5 mmol) are dissolved in dichloromethane (30 mL) and cooled to 0° C. The acid chloride solution is added to this mixture at 0° C. and stirred at room temperature for 2 h. The reaction mixture is diluted with CH2Cl2, washed with brine, dried over Na2SO4, and evaporated. The crude product is purified by silica-gel column chromatography (CH2Cl2:2M NH3 in MeOH=40:1) to give 1.35 g (80%) of the title compound. MS (APCI+) 321 (M+H)+.

Workup

customThe excess thionyl chloride is removed in vacuo
dissolutionthe residue is dissolved in dichloromethane (2 mL)
temperaturecooled to 0° C
stirringstirred at room temperature for 2 h
washwashed with brine
dry with materialdried over Na2SO4
customevaporated
customThe crude product is purified by silica-gel column chromatography (CH2Cl2:2M NH3 in MeOH=40:1)

Sources & evidence

ORD record: ord-14b8e348f16546959eea83df856b87c3
Source dataset: uspto-grants-2011_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08008296B2

Reaction notes

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