2-(Dimethylamino)ethanol → (2R)-1-acetoxy-2-((4S)-2-(3-acetoxy-2-methylphenyl)-4,5-dihydrooxazol-4-yl)-2-methanesulfonyloxyethane

HRID 368802Notes

Reaction equation

HRID 368802 reaction equation
[CH3:1][S:2]([O:5][C@@H:6]1[C@@H:12]([NH:13][C:14](=[O:26])[C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([O:21][C:22](=[O:24])[CH3:23])[C:16]=2[CH3:25])[CH2:11][O:10][C:9]([CH3:28])(C)[O:8][CH2:7]1)(=[O:4])=[O:3].B(F)(F)F.CCOCC.C(OC(=O)C)(=O)C.CN(C)CCO>ClCCl.O.C1(C)C=CC=CC=1>[C:9]([O:8][CH2:7][C@@H:6]([C@@H:12]1[CH2:11][O:26][C:14]([C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([O:21][C:22](=[O:24])[CH3:23])[C:16]=2[CH3:25])=[N:13]1)[O:5][S:2]([CH3:1])(=[O:4])=[O:3])(=[O:10])[CH3:28]

Participants

8

Reactant 4

HCID 79022-(Dimethylamino)ethanolHCID 7918Acetic AnhydrideHCID 8000Boron trifluoride etherateHCID 10787996(5R,6S)-N-(5-methanesulfonyloxy-2,2-dimethyl-1,3-dioxepan-6-yl)-3-acetoxy-2-methylbenzamide2×

Product 1

HCID 10524958(2R)-1-acetoxy-2-((4S)-2-(3-acetoxy-2-methylphenyl)-4,5-dihydrooxazol-4-yl)-2-methanesulfonyloxyethane

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 1140TolueneSolventHCID 6344DichloromethaneSolvent

Procedure

(5R, 6S)-N-(5-Methanesulfonyloxy-2,2-dimethyl-1,3-dioxepan-6-yl)-3-acetoxy-2-methylbenzamide (compound [9], 786 g, 1.89 mol) was dissolved in dichloromethane (6.29 L), and boron trifluoride diethyl ether (698 ml, 5.68 mol) was added, which was followed by stirring at room temperature for 23 hours. The reaction mixture was cooled to 11° C. and acetic anhydride (268 ml, 2.84 mol) was added, which was followed by stirring at said temperature for 2 hours. The reaction mixture was concentrated to 2.0 kg under reduced pressure and toluene (3.8 L) was added to the obtained residue to give a suspension. N,N-Dimethylethanolamine (571 ml, 5.68 mol) was added to the suspension over 40 minutes at not more than 20° C. Toluene (1.5 L) and water (4.8 L) were added and the mixture was stirred for one hour at room temperature. The organic layer was separated, washed successively with a 10% aqueous citric acid solution (5.00 L) and a 2% aqueous potassium carbonate solution (5.00 L) and dried over magnesium sulfate. The desiccant was filtered off and the filtrate was concentrated under reduced pressure to give (2R)-1-acetoxy-2-((4S)-2-(3-acetoxy-2-methylphenyl)-4,5-dihydrooxazol-4-yl)-2-methanesulfonyloxyethane (compound [10'], 1.04 kg) as a dark red oil.

Workup

  1. temperatureThe reaction mixture was cooled to 11° C.
  2. stirringby stirring
  3. customfor 2 hours
  4. concentrationThe reaction mixture was concentrated to 2.0 kg under reduced pressure and toluene (3.8 L)
  5. additionwas added to the obtained residue
  6. customto give a suspension
  7. stirringthe mixture was stirred for one hour at room temperature
  8. customThe organic layer was separated
  9. washwashed successively with a 10% aqueous citric acid solution (5.00 L)
  10. dry with materiala 2% aqueous potassium carbonate solution (5.00 L) and dried over magnesium sulfate
  11. filtrationThe desiccant was filtered off
  12. concentrationthe filtrate was concentrated under reduced pressure

Sources & evidence

ORD record
ord-cce52d3d035d4a18bd7c03fc7b08691c
Source dataset
uspto-grants-2000_10
Patent number
US06133461

Reaction notes

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