Water → HCID 67542568, compound

HRID 1809790Notes

Reaction equation

[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C@H:11]([C:14]2[CH:15]=[C:16]([C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)[CH:17]=[CH:18][CH:19]=2)[C@@H:10]([OH:26])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].Br[CH2:30][C:31]1[CH:40]=[CH:39][C:38]2[C:33](=[CH:34][CH:35]=[CH:36][CH:37]=2)[CH:32]=1.O>CC(N(C)C)=O>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C@H:11]([C:14]2[CH:15]=[C:16]([C:20]3[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=3)[CH:17]=[CH:18][CH:19]=2)[C@@H:10]([O:26][CH2:30][C:31]2[CH:40]=[CH:39][C:38]3[C:33](=[CH:34][CH:35]=[CH:36][CH:37]=3)[CH:32]=2)[CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

Conditions

Temperature: 50 °C

Procedure

A suspension of the title B compound, (3R*,4R*)-4-biphenyl-3-yl-3-hydroxy-piperidine-1-carboxylic acid t-butyl ester (318 mg, 0.9 mmol) and sodium hydride (60% dispersion in mineral oil, 72 mg, 1.8 mmol) in 8 mL of dry DMA is shaken for 10 min. at 50° C. After cooling to RT, 2-(bromomethyl)naphthalene (298 mg, 1.35 mmol) is added and the mixture shaken for 16 h at 50° C. After addition of H2O, the aqueous layer is extracted twice with ethyl acetate. The combined organic extracts are dried (Na2SO4) and evaporated in vacuo. Flash chromatography of the residue (SiO2, hexane/ethyl acetate) affords (3R*,4R*)-4-biphenyl-3-yl-3-(naphthalen-2-ylmethoxy)-piperidine-1-carboxylic acid tert-butyl ester as a yellowish viscous oil: MS (LC/MS) 494.2 [M+H]+; Rf 0.30 (hexane/ethyl acetate 8:2).

Workup

temperatureAfter cooling to RT
stirringthe mixture shaken for 16 h at 50° C
extractionthe aqueous layer is extracted twice with ethyl acetate
dry with materialThe combined organic extracts are dried (Na2SO4)
customevaporated in vacuo

Sources & evidence

ORD record: ord-107aef32c11e452cac5d7298996ad455
Source dataset: uspto-grants-2013_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08362040B2

Reaction notes

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