Sodium hydride → tert-butyl{1-[2-(5,7-difluoro-2-oxoquinoxalin-1(2H)-yl)ethyl]piperidin-4-yl}carbamate

HRID 1644488Notes

Reaction equation

HRID 1644488 reaction equation
[F:1][C:2]1[CH:11]=[C:10]([F:12])[CH:9]=[C:8]2[C:3]=1[N:4]=[CH:5][C:6](=[O:13])[NH:7]2.FC1C=C2C(=C(F)C=1)NC(=O)C=N2.[H-].[Na+].CS(O[CH2:34][CH2:35][N:36]1[CH2:41][CH2:40][CH:39]([NH:42][C:43]([O:45][C:46]([CH3:49])([CH3:48])[CH3:47])=[O:44])[CH2:38][CH2:37]1)(=O)=O.C(OC(=O)NC1CCN(CCN2C3C(=CC=C(OC)C=3)C=CC2=O)CC1)(C)(C)C>C(OCC)C>[C:46]([O:45][C:43](=[O:44])[NH:42][CH:39]1[CH2:40][CH2:41][N:36]([CH2:35][CH2:34][N:7]2[C:8]3[C:3](=[C:2]([F:1])[CH:11]=[C:10]([F:12])[CH:9]=3)[N:4]=[CH:5][C:6]2=[O:13])[CH2:37][CH2:38]1)([CH3:49])([CH3:48])[CH3:47]

Participants

7

Reactant 5

HCID 24758Sodium hydrideHCID 568344782-(4-((Tert-butoxycarbonyl)amino)piperidin-1-yl)ethyl methanesulfonate2×HCID 59371209tert-butyl {1-[2-(7-methoxy-2-oxoquinolin-1(2H)-yl)ethyl]piperidin-4-yl}carbamateHCID 667745755,7-difluoroquinoxalin-2(1H)-oneHCID 667748456,8-difluoroquinoxalin-2(1H)-one2×

Product 1

HCID 86642657tert-butyl{1-[2-(5,7-difluoro-2-oxoquinoxalin-1(2H)-yl)ethyl]piperidin-4-yl}carbamate

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent

Procedure

A mixture of 5,7-difluoroquinoxalin-2(1H)-one and 6,8-difluoroquinoxalin-2(1H)-one (Intermediate 195) (1.05 g, 5.77 mmol) was deprotonated with sodium hydride (0.31 g, 60% in oil, 7.75 mmol) and alkylated with 2-{4-[tert-butoxycarbonyl)amino]piperidin-1-yl}ethyl methanesulfonate (Intermediate 6) (5.8 mmol) as described for Intermediate 2. The residue obtained after aqueous workup was titurated in diethyl ether and filtered yielding 0.73 g of tert-butyl{1-[2-(5,7-difluoro-2-oxoquinoxalin-1(2H)-yl)ethyl]piperidin-4-yl}carbamate (Intermediate 193). The filtrate was concentrated and the residue was purified by chromatography on silica gel with 0-20% acetone in dichloromethane to yield 111 mg of tert-butyl{1-[2-(6,8-difluoro-2-oxoquinoxalin-1(2H)-yl)ethyl]piperidin-4-yl}carbamate (Intermediate 194).

Workup

  1. customThe residue obtained after aqueous workup
  2. filtrationfiltered

Sources & evidence

ORD record
ord-21071f21f42f42c8950900cb5d428479
Source dataset
uspto-grants-2012_02
Patent number
US08124602B2

Reaction notes

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