Oxalyl chloride → (S)-4-[(1R,2R)-2-tert-butyldiphenylsilanyloxy-1-(3,4,5-trifluorophenyl)propyl]-6-methylmorpholine-2,3-dione

HRID 1436112Notes

Reaction equation

HRID 1436112 reaction equation
[C:1](Cl)(=[O:5])[C:2](Cl)=[O:3].[Si:7]([O:24][C@H:25]([CH3:41])[C@H:26]([NH:36][CH2:37][C@@H:38]([OH:40])[CH3:39])[C:27]1[CH:32]=[C:31]([F:33])[C:30]([F:34])=[C:29]([F:35])[CH:28]=1)([C:20]([CH3:23])([CH3:22])[CH3:21])([C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1>CN(C1C=CN=CC=1)C.C(Cl)Cl>[Si:7]([O:24][C@H:25]([CH3:41])[C@H:26]([N:36]1[CH2:37][C@H:38]([CH3:39])[O:40][C:2](=[O:3])[C:1]1=[O:5])[C:27]1[CH:32]=[C:31]([F:33])[C:30]([F:34])=[C:29]([F:35])[CH:28]=1)([C:20]([CH3:22])([CH3:23])[CH3:21])([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1

Participants

5

Reactant 2

HCID 65578Oxalyl chlorideHCID 68718733(S)-1-[(1R,2R)-2-tert-butyldiphenylsilanyloxy-1-(3,4,5-trifluorophenyl)propylamino]propan-2-ol

Product 1

HCID 68718625(S)-4-[(1R,2R)-2-tert-butyldiphenylsilanyloxy-1-(3,4,5-trifluorophenyl)propyl]-6-methylmorpholine-2,3-dione

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

Oxalyl chloride (45 μl) was added dropwise to a solution of (S)-1-[(1R,2R)-2-tert-butyldiphenylsilanyloxy-1-(3,4,5-trifluorophenyl)propylamino]propan-2-ol (171 mg), TEA (0.17 ml), and 4-(N,N-dimethylamino)pyridine (8 mg) in methylene chloride (2 ml) under ice-cooling in a nitrogen atmosphere, and the reaction solution was stirred at the same temperature for two hours. Ice water was added to the reaction solution, followed by extraction with ethyl acetate. Then, the organic layer was sequentially washed with water, 1 N hydrochloric acid, water, a saturated sodium bicarbonate solution, and brine. The organic layer was dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The resulting residue was purified by silica gel column chromatography (heptane:ethyl acetate=9:1 to 3:1) to obtain 96 mg of the title compound.

Workup

  1. temperaturecooling in a nitrogen atmosphere
  2. extractionfollowed by extraction with ethyl acetate
  3. washThen, the organic layer was sequentially washed with water, 1 N hydrochloric acid, water
  4. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
  5. customthe solvent was evaporated under reduced pressure
  6. customThe resulting residue was purified by silica gel column chromatography (heptane:ethyl acetate=9:1 to 3:1)

Sources & evidence

ORD record
ord-2f476e5263f449adbcdeebefd950fa49
Source dataset
uspto-grants-2009_11
Patent number
US07618960B2

Reaction notes

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