Potassium Carbonate → Cis(+/-)1-{2-[4-azido-3-hydroxypiperidin-1-yl]ethyl}-5,7-difluoroquinolin-2(1H)-one

HRID 1644321Notes

Reaction equation

[F:1][C:2]1[CH:11]=[C:10]([F:12])[CH:9]=[C:8]2[C:3]=1[CH:4]=[CH:5][C:6](=[O:13])[NH:7]2.[H-].[Na+].CS(O[CH2:21][CH2:22][N:23]1[CH2:28][CH2:27][C@H:26]([N:29]=[N+:30]=[N-:31])[C@H:25]([OH:32])[CH2:24]1)(=O)=O.C(OC(=O)NC1CCN(CCN2C3C(=CC=C(F)C=3F)C=CC2=O)CC1)(C)(C)C.C(=O)([O-])[O-].[K+].[K+]>>[N:29]([C@H:26]1[CH2:27][CH2:28][N:23]([CH2:22][CH2:21][N:7]2[C:8]3[C:3](=[C:2]([F:1])[CH:11]=[C:10]([F:12])[CH:9]=3)[CH:4]=[CH:5][C:6]2=[O:13])[CH2:24][C@H:25]1[OH:32])=[N+:30]=[N-:31]

Participants

Reactant 5

HCID 11430Potassium Carbonate

HCID 24758Sodium hydride

HCID 642082495,7-Difluoro-1,2-dihydroquinolin-2-one2×

HCID 86642603tert-butyl{1-[2-(7,8-difluoro-2-oxoquinolin-1(2H)-yl)ethyl]piperidin-4-yl}carbamate

HCID 86642609Cis(+/-)2-(4-azido-3-hydroxypiperidin-1-yl)ethyl methanesulfonate2×

Product 1

HCID 86642608Cis(+/-)1-{2-[4-azido-3-hydroxypiperidin-1-yl]ethyl}-5,7-difluoroquinolin-2(1H)-one

Procedure

5,7-Difluoroquinolin-2(1H)-one (Intermediate 25) (389 mg, 2.15 mmol) was deprotonated with sodium hydride (95 mg, 60% in oil, 2.36 mmol) and alkylated with cis(±) 2-(4-azido-3-hydroxypiperidin-1-yl)ethyl methanesulfonate (Intermediate 44) (2.15 mmol) as described for Intermediate 20, except after 24 hours, potassium carbonate (100 mg, 0.72 mmol) was added and the resulting mixture was stirred for another 24 hours at room temperature to give the product as a colorless hard foam, 195 mg (26%).

Sources & evidence

ORD record: ord-8a4f247b2a5e49db9d4b7d4321aefc51
Source dataset: uspto-grants-2012_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08124602B2

Reaction notes

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