Dimethylformamide → (S)-4-[3-(tert-butyldimethylsilanyloxy)-2-methylpropyl]-6-methyl-4H-benzo[1,4]oxazin-3-one

HRID 2103198Notes

Reaction equation

HRID 2103198 reaction equation
[CH3:1][C:2]1[CH:3]=[CH:4][C:5]2[O:10][CH2:9][C:8](=[O:11])[NH:7][C:6]=2[CH:12]=1.Br[CH2:14][C@H:15]([CH3:25])[CH2:16][O:17][Si:18]([C:21]([CH3:24])([CH3:23])[CH3:22])([CH3:20])[CH3:19].C([O-])([O-])=O.[Cs+].[Cs+].CN(C=O)C>CCOCC>[Si:18]([O:17][CH2:16][C@@H:15]([CH3:25])[CH2:14][N:7]1[C:6]2[CH:12]=[C:2]([CH3:1])[CH:3]=[CH:4][C:5]=2[O:10][CH2:9][C:8]1=[O:11])([C:21]([CH3:22])([CH3:23])[CH3:24])([CH3:19])[CH3:20]

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 10796Cesium carbonateHCID 27638392H-1,4-Benzoxazine-3(4H)-one, 6-methyl-HCID 14608666HCID 14608666, compound

Product 1

HCID 68909987(S)-4-[3-(tert-butyldimethylsilanyloxy)-2-methylpropyl]-6-methyl-4H-benzo[1,4]oxazin-3-oneYield 88%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent

Conditions

Temperature
50 °C

Procedure

A dry 50 mL r-flask was charged with 6-Methyl-4H-benzo[1,4]oxazin-3-one (0.59 g, 3.6 mmol), (R)-(3-bromo-2-methylpropoxy)-tert-butyldimethylsilane (1.0 g, 3.6 mmol), Cs2CO3 (2.9 g, 8.9 mmol) and 10 mL of dry DMF. The mixture was stirred at 50° C. overnight (15 h) and dissolved in ether (50 mL) washed with water (20 mL) and the water phase was extracted with ether (20 mL). The combined organic phases were then washed with brine, dried (Na2SO4), filtered, concentrated under reduced pressure and the resulting oil was purified by flash chromatography (SiO2; Heptane/EtOAc 85:15) to yield the title compound as an oil (1.1 g, 88%). 1H NMR (CDCl3) δ 6.87 (d, J=1.6 Hz, 1H), 6.81 (d, J=8.0 Hz, 1H), 6.72 (dm, J=8.0 Hz, 1H), 4.5 (bars, 2H), 3.93 (dd, J=8.8, 14.0 Hz, 1H), 3.81 (dd, J=5.6, 14.0 Hz, 1H), 3.53 (dd, J=4.8, 10.2 Hz, 1H), 3.41 (dd J=7.2, 10.2 Hz, 1H), 2.25 (s, 3H), 2.18 (m, 1H), 0.87 (s, 9H), 0.83 (d, J=6.8 Hz, 3H), 0.01 (s, 6H); 13C NMR (CDCl3) δ 170.5, 148.9, 137.8, 129.6, 122.2, 121.6, 73.3, 71.6, 49.0, 39.7, 31.5, 26.6, 23.8, 20.1, 0.0.

Workup

  1. washwashed with water (20 mL)
  2. extractionthe water phase was extracted with ether (20 mL)
  3. washThe combined organic phases were then washed with brine
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customthe resulting oil was purified by flash chromatography (SiO2; Heptane/EtOAc 85:15)

Sources & evidence

ORD record
ord-397130bbd1cf4d15bf4c9a25efa97545
Source dataset
uspto-grants-2009_08
Patent number
US07576100B2

Reaction notes

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