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

HRID 1016694Notes

Reaction equation

HRID 1016694 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. 1H-NMR (CDCl3, 300 MHz) δ: 7.68 (d,1H,J=7.7 Hz), 7.26 (t,1H,J=7.9 Hz), 7.14 (d,1H,J=8.0 Hz), 5.02 (dt,1H,J=7.7,3.7 Hz), 4.66 (ddd,1H, J=3.6,8.1,9.5 Hz), 4.53 (dd,1H,J=3.3,12.4 Hz), 4.47-4.38 (m,3H), 3.11 (s,3H), 2.40 (s,3H), 2.34 (s,3H), 2.10 (2,3H)

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-6cd43a407fc847f8990cc766e151d3a7
Source dataset
uspto-grants-2002_11
Patent number
US06476232B2

Reaction notes

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