Lithium Hexamethyldisilazide → tert-butyl{1-[2-(7-methoxy-2-oxo-2H-3,1-benzoxazin-1(4H)-yl)ethyl]piperidin-4-yl}carbamate

HRID 1644391Notes

Reaction equation

HRID 1644391 reaction equation
C[O:2]C1C=C2C(C=CC(=O)N2)=CC=1.C[Si]([N-][Si](C)(C)C)(C)C.[Li+].CS(OCCN1CCC(NC(OC(C)(C)C)=O)CC1)(=O)=O.[C:45]([O:49][C:50](=[O:73])[NH:51][CH:52]1[CH2:57][CH2:56][N:55]([CH2:58][CH2:59][N:60]2[C:69]3[C:64](=[CH:65][CH:66]=[C:67]([O:70][CH3:71])[CH:68]=3)[CH:63]=C[C:61]2=[O:72])[CH2:54][CH2:53]1)([CH3:48])([CH3:47])[CH3:46]>CN(C)C=O.ClCCl.CO>[C:45]([O:49][C:50](=[O:73])[NH:51][CH:52]1[CH2:57][CH2:56][N:55]([CH2:58][CH2:59][N:60]2[C:69]3[CH:68]=[C:67]([O:70][CH3:71])[CH:66]=[CH:65][C:64]=3[CH2:63][O:72][C:61]2=[O:2])[CH2:54][CH2:53]1)([CH3:48])([CH3:47])[CH3:46]

Participants

7

Reactant 4

HCID 2733832Lithium HexamethyldisilazideHCID 299427567-Methoxy-1,2-dihydroquinolin-2-one2×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 86642631tert-butyl{1-[2-(7-methoxy-2-oxo-2H-3,1-benzoxazin-1(4H)-yl)ethyl]piperidin-4-yl}carbamateYield 47%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 21226129Dichloromethane methanolSolvent

Procedure

A solution of 7-methoxyquinolin-2(1H)-one (Intermediate 108, 310 mg, 1.8 mmol) in dry N,N-dimethylformamide (5 mL) was treated at 0° C. under stirring with lithium bis(trimethylsilyl)amide (1M in tetrahydrofuran, 1.9 mL, 1.9 mmol). The mixture was then stirred for 30 minutes at room temperature and alkylated with 2-{4-[(tert-butoxycarbonyl)amino]piperidin-1-yl}ethyl methanesulfonate (Intermediate 6, 2.03 mmol) as described for Intermediate 2. Chromatography on silica gel with dichloromethane/methanol (95:5) gave 333 mg (47%) of the product as a colorless solid.

Sources & evidence

ORD record
ord-9856fccb8802467fb6a340c483da4490
Source dataset
uspto-grants-2012_02
Patent number
US08124602B2

Reaction notes

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