Methyl iodide → (S)-[1-[1-(4-Chloro-phenyl)-cyclobutylmethyl]-3-(2-methoxy-2-phenyl-ethyl) piperidine]

HRID 2110319Notes

Reaction equation

ClC1C=CC(C2(CN3CCCC(C[C@@H](C4C=CC=CC=4)O)C3)CCC2)=CC=1.CC(C)([O-])C.[K+].CI.[OH-].[NH4+].[Cl:38][C:39]1[CH:44]=[CH:43][C:42]([C:45]2([CH2:49][N:50]3[CH2:55][CH2:54][CH2:53][CH:52]([CH2:56][CH:57]([O:64][CH3:65])[C:58]4[CH:63]=[CH:62][CH:61]=[CH:60][CH:59]=4)[CH2:51]3)[CH2:48][CH2:47][CH2:46]2)=[CH:41][CH:40]=1>C1COCC1.CCOC(C)=O.CCCCCC.CCOCC.O>[Cl:38][C:39]1[CH:44]=[CH:43][C:42]([C:45]2([CH2:49][N:50]3[CH2:55][CH2:54][CH2:53][C@@H:52]([CH2:56][CH:57]([O:64][CH3:65])[C:58]4[CH:59]=[CH:60][CH:61]=[CH:62][CH:63]=4)[CH2:51]3)[CH2:48][CH2:47][CH2:46]2)=[CH:41][CH:40]=1

Participants

Conditions

Temperature: 0 °C

Procedure

(S)-[2-{-[1-(4-Chloro-phenyl)-cyclobutylmethyl]-piperidin-3-yl}-1-phenyl-ethanol] (38 mg, 0.100 mmol) was dissolved in 1 mL of THF and cooled to 0° C. Potassium tert-butoxide was added (112 mg, 1.0 mmol) followed by methyl iodide in large excess (ca. 0.5 mL). After 30 minutes at 0° C., water (5 mL) and ether (5 mL) were added. Extractive workup gave, after concentration of the organic layers in vacuo and chromatography on silica gel using as eluent an EtOAc-hexane gradient with 1% ammonium hydroxide, the desired product 1-[1-(4-Chloro-phenyl)-cyclobutylmethyl]-3-(2-methoxy-2-phenyl-ethyl)-piperidine, 184, (28 mg, 70%). Data for this compound: MS 398 (M++1).

Workup

customExtractive workup gave

Sources & evidence

ORD record: ord-42101b6963ee4e1899500252d3f35db2
Source dataset: uspto-grants-2009_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07517892B2

Reaction notes

Loading…