Triethylamine → (R)-9-(triisopropylsilyloxy)-6,7,8,9-tetrahydro-5H-cyclohepta[b]pyridin-5-one

HRID 1666138Notes

Reaction equation

[OH:1][C@H:2]1[C:8]2=[N:9][CH:10]=[CH:11][CH:12]=[C:7]2[C:6](=[O:13])[CH2:5][CH2:4][CH2:3]1.[Si:14](OS(C(F)(F)F)(=O)=O)([CH:21]([CH3:23])[CH3:22])([CH:18]([CH3:20])[CH3:19])[CH:15]([CH3:17])[CH3:16].CCN(CC)CC>C(Cl)Cl>[CH:15]([Si:14]([CH:21]([CH3:23])[CH3:22])([CH:18]([CH3:20])[CH3:19])[O:1][C@H:2]1[C:8]2=[N:9][CH:10]=[CH:11][CH:12]=[C:7]2[C:6](=[O:13])[CH2:5][CH2:4][CH2:3]1)([CH3:17])[CH3:16]

Participants

Conditions

Temperature: 0 °C

Procedure

In a 1L round-bottomed flask was (R)-9-hydroxy-6,7,8,9-tetrahydro-5H-cyclohepta[b]pyridin-5-one (19.14 g, 108 mmol) (azeotroped with dry benzene) in CH2Cl2 (300 mL) to give a tan solution. After cooling to 0° C., TIPS-OTf (29.3 mL, 108 mmol) and Et3N (30.1 mL, 216 mmol) were added via syringe, and the mixture was stirred at 0° C. for 1h. LCMS indicated complete conversion. Volatiles were stripped off and the residue was partitioned between NaHCO3 solution and EtOAc. The layers were separated and the organic layer was washed with brine, dried and concentrated to a tan oil (37 g). It was purified by FCC up to 20% EtOAc/hexane to afford the product as a white solid (26.3 g, 73% for two steps). MS(ESI)[M+H+]=334.37.

Workup

customto give a tan solution
customthe residue was partitioned between NaHCO3 solution and EtOAc
customThe layers were separated
washthe organic layer was washed with brine
customdried
concentrationconcentrated to a tan oil (37 g)
customIt was purified by FCC up to 20% EtOAc/hexane

Sources & evidence

ORD record: ord-9f83e674f13d41f5b8bb4a53e4bb6824
Source dataset: uspto-grants-2011_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08044043B2

Reaction notes

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