Water → [1-(5-Acetyl-pyridin-2-yl)-cyclopropyl]-carbamic acid tert-butyl ester

HRID 1040501Notes

Reaction equation

[C:1]([O:5][C:6](=[O:18])[NH:7][C:8]1([C:11]2[CH:16]=[CH:15][C:14](I)=[CH:13][N:12]=2)[CH2:10][CH2:9]1)([CH3:4])([CH3:3])[CH3:2].C([Sn](CCCC)(CCCC)[C:24]([O:26]CC)=[CH2:25])CCC.C1(C)C=CC(S([O-])(=O)=O)=CC=1.[NH+]1C=CC=CC=1.O>CN(C=O)C.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>[C:1]([O:5][C:6](=[O:18])[NH:7][C:8]1([C:11]2[CH:16]=[CH:15][C:14]([C:24](=[O:26])[CH3:25])=[CH:13][N:12]=2)[CH2:10][CH2:9]1)([CH3:4])([CH3:3])[CH3:2]

Participants

Conditions

Temperature: 100 °C

Procedure

To a solution of [1-(5-Iodo-pyridin-2-yl)-cyclopropyl]-carbamic acid tert-butyl ester (100 mg, 0.278 mmol) in anhydrous DMF (1 mL) was added tributyl-(1-ethoxy-vinyl)-stannane (0.103 mL, 0.305 mmol) followed by tetrakis(triphenylphosphane)palladium (0) (32.1 mg, 0.028 mmol). The mixture was stirred at 100° C. under an atmosphere of argon. After 16 h, pyridinium p-toluenesulfonate (77.0 mg, 0.306 mmol) was added along with 0.5 mL of water and the mixture was stirred at rt for 1 h. The reaction was diluted with 10 mL of 10% citric acid and was extracted with EtOAc (3×30 mL). The combined organic layers were washed with brine, dried over MgSO4, filtered, and concentrated in vacuo. The product was purified by column chromatography (10 g biotage SNAP column, 5-40% EtOAc in hexanes) to give the title compound as a yellow solid (74.7 mg, 97%).

Workup

stirringthe mixture was stirred at rt for 1 h
extractionwas extracted with EtOAc (3×30 mL)
washThe combined organic layers were washed with brine
dry with materialdried over MgSO4
filtrationfiltered
concentrationconcentrated in vacuo
customThe product was purified by column chromatography (10 g biotage SNAP column, 5-40% EtOAc in hexanes)

Sources & evidence

ORD record: ord-b8e49c1734f7423e9d34bbe878d4ff6f
Source dataset: uspto-grants-2013_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08552205B2

Reaction notes

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