Dimethyl Sulfoxide → (3R,5R)-3-acetyl-5-(3,4,5-trifluorophenyl)morpholine-4-carboxylic acid benzyl ester

HRID 16389Notes

Reaction equation

HRID 16389 reaction equation
CS(C)=O.C(Cl)(=O)C(Cl)=O.[CH2:11]([O:18][C:19]([N:21]1[C@H:26]([C:27]2[CH:32]=[C:31]([F:33])[C:30]([F:34])=[C:29]([F:35])[CH:28]=2)[CH2:25][O:24][CH2:23][C@@H:22]1[C@H:36]([OH:38])[CH3:37])=[O:20])[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.C(N(CC)CC)C>O1CCCC1.[Cl-].[NH4+].C(OCC)(=O)C>[CH2:11]([O:18][C:19]([N:21]1[C@H:26]([C:27]2[CH:32]=[C:31]([F:33])[C:30]([F:34])=[C:29]([F:35])[CH:28]=2)[CH2:25][O:24][CH2:23][C@@H:22]1[C:36](=[O:38])[CH3:37])=[O:20])[C:12]1[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=1

Participants

8

Reactant 4

HCID 679Dimethyl SulfoxideHCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 67373415(3R,5R)-3-((R)-1-hydroxyethyl)-5-(3,4,5-trifluorophenyl)morpholine-4-carboxylic acid benzyl ester

Product 1

HCID 67372176(3R,5R)-3-acetyl-5-(3,4,5-trifluorophenyl)morpholine-4-carboxylic acid benzyl esterYield 91.4%

Reagents, catalysts & solvents 3

HCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolventHCID 25517Ammonium ChlorideSolvent

Procedure

A solution of dimethylsulfoxide (0.22 mL) in tetrahydrofuran (15 mL) was cooled to −78° C. and then oxalyl chloride (246 μL) was dropwise added thereto. The resultant solution was stirred at the same temperature for 5 minutes, and to the reaction mixture was then dropwise added a solution of (3R,5R)-3-((R)-1-hydroxyethyl)-5-(3,4,5-trifluorophenyl)morpholine-4-carboxylic acid benzyl ester (880 mg) in tetrahydrofuran (5 mL). The resultant solution was stirred at the same temperature for 1 hour, and triethylamine (1.54 mL) was then added thereto. The temperature of this solution was returned to room temperature. The solution was then stirred for 1 hour. The reaction solution was diluted with aqueous ammonium chloride and ethyl acetate, and the organic layer was partitioned. The organic layer was dried over anhydrous magnesium sulfate. Solvent was removed by distillation under reduced pressure. The resultant product was purified by silica gel column chromatography (heptane/ethyl acetate), to thereby obtain the titled compound (800 mg). The physical properties of this crude product were as follows.

Workup

  1. customwas returned to room temperature
  2. customthe organic layer was partitioned
  3. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
  4. customSolvent was removed by distillation under reduced pressure
  5. customThe resultant product was purified by silica gel column chromatography (heptane/ethyl acetate)

Sources & evidence

ORD record
ord-735ee56b53ef437abd150beb32c328a5
Source dataset
uspto-grants-2010_06
Patent number
US07737141B2

Reaction notes

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