Sodium hydride → Methyl 4-(2-{4-[(tert-butoxycarbonyl)amino]piperidin-1-yl}ethyl)-3-oxo-3,4-dihydro-2H-1,4-benzoxazine-6-carboxylate

HRID 255245Notes

Reaction equation

HRID 255245 reaction equation
[O:1]=[C:2]1[NH:7][C:6]2[CH:8]=[C:9]([C:12]([O:14][CH3:15])=[O:13])[CH:10]=[CH:11][C:5]=2[O:4][CH2:3]1.[H-].[Na+].CS(O[CH2:23][CH2:24][N:25]1[CH2:30][CH2:29][CH:28]([NH:31][C:32]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33])[CH2:27][CH2:26]1)(=O)=O.COC1C=C2C(C=CC(=O)N2CCN2CCC(NC(=O)OC(C)(C)C)CC2)=CC=1>ClCCl.CO>[C:35]([O:34][C:32]([NH:31][CH:28]1[CH2:27][CH2:26][N:25]([CH2:24][CH2:23][N:7]2[C:6]3[CH:8]=[C:9]([C:12]([O:14][CH3:15])=[O:13])[CH:10]=[CH:11][C:5]=3[O:4][CH2:3][C:2]2=[O:1])[CH2:30][CH2:29]1)=[O:33])([CH3:38])([CH3:37])[CH3:36]

Participants

6

Reactant 4

HCID 24758Sodium hydrideHCID 2974054Methyl 3-oxo-3,4-dihydro-2H-1,4-benzoxazine-6-carboxylate2×HCID 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}carbamate

Product 1

HCID 66774852Methyl 4-(2-{4-[(tert-butoxycarbonyl)amino]piperidin-1-yl}ethyl)-3-oxo-3,4-dihydro-2H-1,4-benzoxazine-6-carboxylateYield 85%

Reagents, catalysts & solvents 1

HCID 21226129Dichloromethane methanolSolvent

Procedure

Methyl 3-oxo-3,4-dihydro-2H-1,4-benzoxazine-6-carboxylate (Intermediate 86) (330 mg, 1.59 mmol) was deprotonated with sodium hydride and alkylated with 2-{4-[(tert-butoxycarbonyl)amino]piperidin-1-yl}ethyl methanesulfonate (Intermediate 6) (5.6 mmol) as described for Intermediate 2. Chromatography on silica gel with dichloromethane/methanol (20:1) gave the product in 85% yield as a yellow solid.

Sources & evidence

ORD record
ord-f8d42ec8d1464e19b2abb2d44309fdea
Source dataset
uspto-grants-2011_01
Patent number
US07875715B2

Reaction notes

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