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

HRID 2202806Notes

Reaction equation

[C:1]([O:5][C:6]([N:8]1[CH:13]2[CH2:14][CH2:15][CH:9]1[CH2:10][CH:11]([C:16]#[N:17])[CH2:12]2)=[O:7])([CH3:4])([CH3:3])[CH3:2].Cl[C:19]1[S:20][CH:21]=[CH:22][N:23]=1.[Li].C[Si](N[Si](C)(C)C)(C)C.[Cl-].[NH4+]>C1COCC1>[C:1]([O:5][C:6]([N:8]1[CH:13]2[CH2:14][CH2:15][CH:9]1[CH2:10][C:11]([C:16]#[N:17])([C:19]1[S:20][CH:21]=[CH:22][N:23]=1)[CH2:12]2)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

Conditions

Temperature: -78 °C

Procedure

3-Cyano-8-aza-bicyclo[3.2.1]octane-8-carboxylic acid tert-butyl ester (0.15 g) and 2-chloro-1,3-thiazole (0.09 g, 0.75 mmol) were dissolved in THF (4 mL). The mixture was cooled to −78° C. and lithium HMDS (1 M in THF; 0.89 mL) was added dropwise. After 5 minutes, the mixture was allowed to warm to room temperature and after 0.5 hour saturated aqueous ammonium chloride was added and the products extracted into ethyl acetate. The organic solution was dried with anhydrous magnesium sulphate, filtered and the solvent removed by evaporation. The residue was purified by flash chromatography on silica eluting with 30% ethyl acetate/hexane. The fractions containing the desired product were concentrated under vacuum to give the title compound (0.2 g).

Workup

additionwas added
extractionthe products extracted into ethyl acetate
dry with materialThe organic solution was dried with anhydrous magnesium sulphate
filtrationfiltered
customthe solvent removed by evaporation
customThe residue was purified by flash chromatography on silica eluting with 30% ethyl acetate/hexane
additionThe fractions containing the desired product
concentrationwere concentrated under vacuum

Sources & evidence

ORD record: ord-daab8150e08141359e7293f4f8193941
Source dataset: uspto-grants-2016_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09365564B2

Reaction notes

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