Sodium hydride → 3-[(4-Bromo-phenyl)-methoxy-methylene]-8-pyrimidin-2-yl-8-aza-bicyclo[3.2.1]octane

HRID 1619219Notes

Reaction equation

C(OP([CH:9]([C:12]1[CH:17]=[CH:16][C:15]([Br:18])=[CH:14][CH:13]=1)[O:10][CH3:11])(=O)OCC)C.[H-].[Na+].[N:21]1[CH:26]=[CH:25][CH:24]=[N:23][C:22]=1[N:27]1[CH:32]2[CH2:33][CH2:34][CH:28]1[CH2:29][C:30](=O)[CH2:31]2>COCCOC>[Br:18][C:15]1[CH:14]=[CH:13][C:12]([C:9]([O:10][CH3:11])=[C:30]2[CH2:31][CH:32]3[N:27]([C:22]4[N:21]=[CH:26][CH:25]=[CH:24][N:23]=4)[CH:28]([CH2:34][CH2:33]3)[CH2:29]2)=[CH:17][CH:16]=1

Participants

Conditions

Temperature: 50 °C

Procedure

To a solution of [(4-bromo-phenyl)-methoxy-methyl]-phosphonic acid diethyl ester (4.58 g, 13.5 mmol) in 1,2-dimethoxy-ethane (60 ml), was added NaH (540 mg, 13.5 mmol, 60% in mineral oil) in one portion. The mixture was stirred at 50° C. for 1.5 hrs before it was added by 8-pyrimidin-2-yl-8-aza-bicyclo[3.2.1]octan-3-one (2.0 g, 9.85 mmol) in 1,2-dimethoxy-ethane (5 ml). The mixture was stirred at 50° C. over the weekend. The resulting mixture was concentrated down and purified by ISCO to afford 3-[(4-bromo-phenyl)-methoxy-methylene]-8-pyrimidin-2-yl-8-aza-bicyclo[3.2.1]octane (600 mg, 30%). The white solid product was used as it was. MS (M+1)=386.

Workup

stirringThe mixture was stirred at 50° C. over the weekend
concentrationThe resulting mixture was concentrated down
custompurified by ISCO

Sources & evidence

ORD record: ord-18eae2920cb246faa10100d160e605d9
Source dataset: uspto-grants-2014_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08772291B2

Reaction notes

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