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

HRID 255272Notes

Reaction equation

HRID 255272 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.[CH3:45][O:46][C:47]1[CH:56]=[C:55]2[C:50]([CH:51]=C[C:53](=[O:73])[N:54]2[CH2:57][CH2:58][N:59]2[CH2:64][CH2:63][CH:62]([NH:65][C:66](=[O:72])[O:67][C:68]([CH3:71])([CH3:70])[CH3:69])[CH2:61][CH2:60]2)=[CH:49][CH:48]=1>CN(C)C=O.ClCCl.CO>[CH3:45][O:46][C:47]1[CH:48]=[CH:49][C:50]2[CH2:51][O:73][C:53](=[O:2])[N:54]([CH2:57][CH2:58][N:59]3[CH2:60][CH2:61][CH:62]([NH:65][C:66](=[O:72])[O:67][C:68]([CH3:71])([CH3:70])[CH3:69])[CH2:63][CH2:64]3)[C:55]=2[CH:56]=1

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-be88672bedeb4c43a67c934ef7fc799c
Source dataset
uspto-grants-2011_01
Patent number
US07875715B2

Reaction notes

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