Methyl iodide → (R)-6-(3-(tert-butyldimethylsilyloxy)propyl)-6-(4-fluorophenyl)-3-((S)-1-(4-(1-methyl-6-oxo-1,6-dihydropyridin-3-yl)phenyl)ethyl)-1,3-oxazinan-2-one

HRID 406677Notes

Reaction equation

HRID 406677 reaction equation
[H-].[Na+].[Si:3]([O:10][CH2:11][CH2:12][CH2:13][C@@:14]1([C:36]2[CH:41]=[CH:40][C:39]([F:42])=[CH:38][CH:37]=2)[O:19][C:18](=[O:20])[N:17]([C@H:21]([C:23]2[CH:28]=[CH:27][C:26]([C:29]3[CH:34]=[CH:33][C:32](=[O:35])[NH:31][CH:30]=3)=[CH:25][CH:24]=2)[CH3:22])[CH2:16][CH2:15]1)([C:6]([CH3:9])([CH3:8])[CH3:7])([CH3:5])[CH3:4].[CH3:43]I>C1COCC1>[Si:3]([O:10][CH2:11][CH2:12][CH2:13][C@@:14]1([C:36]2[CH:37]=[CH:38][C:39]([F:42])=[CH:40][CH:41]=2)[O:19][C:18](=[O:20])[N:17]([C@H:21]([C:23]2[CH:24]=[CH:25][C:26]([C:29]3[CH:34]=[CH:33][C:32](=[O:35])[N:31]([CH3:43])[CH:30]=3)=[CH:27][CH:28]=2)[CH3:22])[CH2:16][CH2:15]1)([C:6]([CH3:7])([CH3:8])[CH3:9])([CH3:4])[CH3:5]

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 59635779(R)-6-(3-(tert-butyldimethylsilyloxy)propyl)-6-(4-fluorophenyl)-3-((S)-1-(4-(6-oxo-1,6-dihydropyridin-3-yl)phenyl)ethyl)-1,3-oxazinan-2-one

Product 1

HCID 59635791(R)-6-(3-(tert-butyldimethylsilyloxy)propyl)-6-(4-fluorophenyl)-3-((S)-1-(4-(1-methyl-6-oxo-1,6-dihydropyridin-3-yl)phenyl)ethyl)-1,3-oxazinan-2-oneYield 100%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a suspension of NaH (18 mg, 0.72 mmol) in THF (0.5 mL) was added a solution of (R)-6-(3-(tert-butyldimethylsilyloxy)propyl)-6-(4-fluorophenyl)-3-((S)-1-(4-(6-oxo-1,6-dihydropyridin-3-yl)phenyl)ethyl)-1,3-oxazinan-2-one (100 mg, 0.18 mmol) in THF (10 mL) at 0° C. The resulting mixture was stirred for 1 h. Then CH3I (613 mg, 43.2 mmol) was added, and the mixture was stirred for 3 h. The reaction was quenched with aq NH4Cl solution. The organic phase was separated, and concentrated to give (R)-6-(3-(tert-butyldimethylsilyloxy)propyl)-6-(4-fluorophenyl)-3-((S)-1-(4-(1-methyl-6-oxo-1,6-dihydropyridin-3-yl)phenyl)ethyl)-1,3-oxazinan-2-one (104 mg, 100%), which was used for the next step without further purification.

Workup

  1. stirringthe mixture was stirred for 3 h
  2. customThe reaction was quenched with aq NH4Cl solution
  3. customThe organic phase was separated
  4. concentrationconcentrated

Sources & evidence

ORD record
ord-ced89991e1494496a461f118a3b7d244
Source dataset
uspto-grants-2014_06
Patent number
US08754076B2

Reaction notes

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