Acetic Acid → trans-(4-Cyclopentylamino-tetrahydro-pyran-3-yl)-carbamic acid tert-butyl ester

HRID 39426Notes

Reaction equation

[C:1]([O:5][C:6](=[O:15])[NH:7][C@H:8]1[C@H:13]([NH2:14])[CH2:12][CH2:11][O:10][CH2:9]1)([CH3:4])([CH3:3])[CH3:2].C(O)(=O)C.[C:20]1(=O)[CH2:24][CH2:23][CH2:22][CH2:21]1.C([BH3-])#N.[Na+]>CO>[C:1]([O:5][C:6](=[O:15])[NH:7][C@H:8]1[C@H:13]([NH:14][CH:20]2[CH2:24][CH2:23][CH2:22][CH2:21]2)[CH2:12][CH2:11][O:10][CH2:9]1)([CH3:4])([CH3:2])[CH3:3]

Participants

Conditions

Temperature: 45 °C

Procedure

trans-(4-Amino-tetrahydro-pyran-3-yl)-carbamic acid tert-butyl ester (intermediate G, 1.0 g, 4.63 mmol) was dissolved in 90 mL methanol. Acetic acid (1.4 g, 23 mmol) and cyclopentanone (1.18 g, 14 mmol) were added and the reaction mixture was stirred at 45° C. overnight. Sodium cyanoborohydride (612 mg, 9.7 mmol) was added and stirring was continued at 45° C. for 2 h. The mixture was extracted with 2N sodium carbonate solution and ethyl acetate. The combined organic phases were dried on sodium sulfate, filtered and evaporated. Purification of the residue by flash chromatography on silica gel (dichloromethane/methanol/ammonia 100:0:0→90:10:1) yielded the title compound as a yellow solid (815 mg, 62%), MS: m/e=229.4 [(M-butene)+].

Workup

stirringstirring
waitwas continued at 45° C. for 2 h
extractionThe mixture was extracted with 2N sodium carbonate solution and ethyl acetate
customThe combined organic phases were dried on sodium sulfate
filtrationfiltered
customevaporated
customPurification of the residue by flash chromatography on silica gel (dichloromethane/methanol/ammonia 100:0:0→90:10:1)

Sources & evidence

ORD record: ord-f6d13372ecf343bda0ef3a8ece003fbc
Source dataset: uspto-grants-2013_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08524909B2

Reaction notes

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