Pyrrolidine → HCID 53628957, compound

HRID 1784717Notes

Reaction equation

[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([C:14]2[CH:19]=[CH:18][C:17](Br)=[CH:16][CH:15]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(P(C(C)(C)C)C1C=CC=CC=1C1C=CC=CC=1)(C)(C)C.CC(C)([O-])C.[Na+].[NH:48]1[CH2:52][CH2:51][CH2:50][CH2:49]1>C1(C)C=CC=CC=1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([C:14]2[CH:19]=[CH:18][C:17]([N:48]3[CH2:52][CH2:51][CH2:50][CH2:49]3)=[CH:16][CH:15]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

Conditions

Temperature: 90 °C

Procedure

A suspension of 4-(4-Bromophenyl)-piperidine-1-carboxylic acid tert-butyl ester (1.97 g, 5.79 mmol), palladium acetate (54 mg, 0.24 mmol), 2-(di-t-butylphosphino)biphenyl (154 mg, 0.52 mmol), and sodium t-butoxide (846 mg, 8.80 mmol), pyrrolidine (587 mg, 8.25 mmol) in toluene (80 mL) was heated at 90° C. for 3 h under nitrogen atmosphere. The resulting suspension was passed through a Celite column and partitioned between ethyl acetate and water. The aqueous layer was extracted with ethyl acetate. The combined organic layer was washed with brine, dried over sodium sulfate, and concentrated in vacuo. Purification of the residue by HPLC afforded 4-(4-pyrrolidin-1-yl-phenyl)-piperidine-1-carboxylic acid tert-butyl ester as a solid that was used in the next step without further purification.

Workup

custompartitioned between ethyl acetate and water
extractionThe aqueous layer was extracted with ethyl acetate
washThe combined organic layer was washed with brine
dry with materialdried over sodium sulfate
concentrationconcentrated in vacuo
customPurification of the residue by HPLC

Sources & evidence

ORD record: ord-fcbbc628771c47e0b6e6fc681d9349d2
Source dataset: uspto-grants-2009_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07504411B2

Reaction notes

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