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

HRID 1923471Notes

Reaction equation

S(Cl)(Cl)=O.[Cl:5][CH2:6][CH2:7][C:8]1[CH:16]=[CH:15][C:11]([C:12]([OH:14])=O)=[CH:10][CH:9]=1.C(N(CC)CC)C.[NH:24]1[CH2:28][CH2:27][CH2:26][C@H:25]1[CH2:29][N:30]1[CH2:34][CH2:33][CH2:32][CH2:31]1>ClCCl>[Cl:5][CH2:6][CH2:7][C:8]1[CH:9]=[CH:10][C:11]([C:12]([N:24]2[CH2:28][CH2:27][CH2:26][C@H:25]2[CH2:29][N:30]2[CH2:34][CH2:33][CH2:32][CH2:31]2)=[O:14])=[CH:15][CH:16]=1

Participants

Conditions

Temperature: 50 °C

Procedure

Add thionylchloride (6 mL) to 4-(2-chloroethyl)benzoic acid (1.00 g, 5.4 mmol) and stir at 50° C. for 30 min. Remove the excess thionylchloride in vacuo and dissolve the reside to dichloromethane (2 mL). Add this acid chloride solution to the mixture of triethylamine (656 mg, 6.5 mmol) and (S)(+)-1-(2-pyrrolidinylmethyl)pyrrolidine (1.00 g, 6.5 mmol) in dichloromethane (30 mL) at 0° C. and stir it at room temperature for 2 h. Dilute the reaction mixture and wash with brine, dry over sodium sulfate and remove the solvent. Purify the crude product by a silica-gel column chromatography (dichloromethane:2M ammonia in methanol=40:1) to give the title compound. 1.35 g (80%). Observed Mass 321.

Workup

customRemove the excess thionylchloride in vacuo
dissolutiondissolve the reside to dichloromethane (2 mL)
additionAdd this acid chloride solution
stirringstir it at room temperature for 2 h
additionDilute the reaction mixture
washwash with brine
dry with materialdry over sodium sulfate
customremove the solvent
customPurify the crude product by a silica-gel column chromatography (dichloromethane:2M ammonia in methanol=40:1)

Sources & evidence

ORD record: ord-d20b3982e36242ddb61d9735bc36994e
Source dataset: uspto-grants-2012_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08178528B2

Reaction notes

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