Ammonium Chloride → 3-Hydroxy-3-pyrimidin-2-yl-8-aza-bicyclo[3.2.1]octane-8-carboxylic acid tert-butyl ester

HRID 2202776Notes

Reaction equation

C([Li])CCC.C([Sn](CCCC)(CCCC)[C:11]1[N:16]=[CH:15][CH:14]=[CH:13][N:12]=1)CCC.[C:25]([O:29][C:30]([N:32]1[CH:37]2[CH2:38][CH2:39][CH:33]1[CH2:34][C:35](=[O:40])[CH2:36]2)=[O:31])([CH3:28])([CH3:27])[CH3:26].[Cl-].[NH4+]>C1COCC1>[C:25]([O:29][C:30]([N:32]1[CH:37]2[CH2:38][CH2:39][CH:33]1[CH2:34][C:35]([OH:40])([C:11]1[N:12]=[CH:13][CH:14]=[CH:15][N:16]=1)[CH2:36]2)=[O:31])([CH3:28])([CH3:26])[CH3:27]

Participants

Conditions

Temperature: -78 °C

Procedure

n-Butyl lithium (2.5M, 1.1 mL, 2.77 mmol) was added dropwise to a solution of 2-tributylstannanyl-pyrimidine (1 g, 2.71 mmol) in THF (5 mL), under nitrogen at −78° C. 3-Oxo-8-aza-bicyclo[3.2.1]octane-8-carboxylic acid tert-butyl ester (0.25 g, 1.13 mmol) in THF (2 mL) was added and the reaction mixture stirred at −78° C. for 3 hours. A solution of saturated aqueous ammonium chloride was added and the mixture extracted into ethyl acetate, dried over magnesium sulphate, filtered and the solvent removed by evaporation under vacuum. The residue was purified by flash chromatography on silica eluting with 5-30% ethyl acetate/cyclohexane. The fractions containing the desired product were concentrated under vacuum to give the title compound (0.14 g). LCMS m/z 306.2 [M+H]+. R.T.=3.44 min (Analytical Method 3).

Workup

extractionthe mixture extracted into ethyl acetate
dry with materialdried over magnesium sulphate
filtrationfiltered
customthe solvent removed by evaporation under vacuum
customThe residue was purified by flash chromatography on silica eluting with 5-30% ethyl acetate/cyclohexane
additionThe fractions containing the desired product
concentrationwere concentrated under vacuum

Sources & evidence

ORD record: ord-c0cd8f5865d54c9aba2c5d043b9cbac7
Source dataset: uspto-grants-2016_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09365564B2

Reaction notes

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