Dichloromethane → N-(3-((R)-3-((S)-1-(4-bromophenyl)ethyl)-2-oxo-6-phenyl-1,3-oxazinan-6-yl)propyl)-N-methylacetamide

HRID 1187797Notes

Reaction equation

HRID 1187797 reaction equation
CS(OC[CH2:7][CH2:8][C@@:9]1([C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[O:14][C:13](=[O:15])[N:12]([C@H:16]([C:18]2[CH:23]=[CH:22][C:21]([Br:24])=[CH:20][CH:19]=2)[CH3:17])[CH2:11][CH2:10]1)(=O)=O.[H-].[Na+].[CH3:33][NH:34][C:35](=[O:37])[CH3:36].[CH2:38](Cl)Cl>>[Br:24][C:21]1[CH:20]=[CH:19][C:18]([C@@H:16]([N:12]2[CH2:11][CH2:10][C@:9]([CH2:8][CH2:7][CH2:33][N:34]([CH3:38])[C:35](=[O:37])[CH3:36])([C:25]3[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=3)[O:14][C:13]2=[O:15])[CH3:17])=[CH:23][CH:22]=1

Participants

5

Reactant 4

HCID 6344DichloromethaneHCID 6582N-MethylacetamideHCID 24758Sodium hydrideHCID 596357093-((R)-3-((S)-1-(4-bromophenyl)ethyl)-2-oxo-6-phenyl-1,3-oxazinan-6-yl)propyl methanesulfonate

Product 1

HCID 59635812N-(3-((R)-3-((S)-1-(4-bromophenyl)ethyl)-2-oxo-6-phenyl-1,3-oxazinan-6-yl)propyl)-N-methylacetamideYield 68%

Procedure

To a solution of 3-((R)-3-((S)-1-(4-bromophenyl)ethyl)-2-oxo-6-phenyl-1,3-oxazinan-6-yl)propyl methanesulfonate (234 mg, 0.24 mmol) in CH2Cl2 (3 mL) was added NaH (82 mg, 3.4 mmol) at 0° C. The mixture was stirred at rt for 30 min. Then N-methylacetamide (204 mg, 2.8 mmol) was added the above mixture. The formed mixture was stirred at 80° C. for 5 h. After the reaction was over, the reaction was quenched with water and the mixture was extracted with EtOAc. The combined organic phase was concentrated to give the crude product, which was purified by preparative TLC to give N-(3-((R)-3-((S)-1-(4-bromophenyl)ethyl)-2-oxo-6-phenyl-1,3-oxazinan-6-yl)propyl)-N-methylacetamide (150 mg, 68%). LC-MS Method 2 tR=1.50 min, m/z=497, 495, 475, 473. 1H NMR (400 MHz, CDCl3): δ=1.41 (m, 1H), 1.48 (t, 3H), 1.73 (m, 1H), 1.83-1.95 (m, 2H), 2.01 (m, 3H), 2.1-2.3 (m, 3H), 2.71 (m, 1H), 2.81 (s, 3H), 3.1 (m, 1H), 3.2 (m, 1H), 5.5 (m, 1H), 6.72 (m, 2H), 7.10 (m, 2H), 7.20 (m, 2H), 7.37 (m, 3H).

Workup

  1. stirringThe formed mixture was stirred at 80° C. for 5 h
  2. customwas quenched with water
  3. extractionthe mixture was extracted with EtOAc
  4. concentrationThe combined organic phase was concentrated
  5. customto give the crude product, which
  6. customwas purified by preparative TLC

Sources & evidence

ORD record
ord-16b60f553e674ec69146a1095fcb7d26
Source dataset
uspto-grants-2014_03
Patent number
US08673899B2

Reaction notes

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