Dichloromethane → 6-chloro-(1S)-camphanoyl-4-phenylethynyl-4-trifluoromethyl-1,4-dihydro-2H-3,1-benzoxazin-2-one

HRID 440264Notes

Reaction equation

HRID 440264 reaction equation
Cl[C:2]1[CH:3]=[CH:4][C:5]2[NH:10][C:9](=[O:11])[O:8][C:7]([C:16]#[C:17][C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)([C:12]([F:15])([F:14])[F:13])[C:6]=2[CH:24]=1.[C:25]12([CH3:37])[C:31]([CH3:33])([CH3:32])[CH:28]([CH2:29][CH2:30]1)[CH2:27][CH:26]2[C:34](Cl)=[O:35].C(N(CC)CC)C.[Cl:45]CCl>CN(C)C1C=CN=CC=1>[Cl:45][CH:30]1[C@:25]2([CH3:37])[C:31]([CH3:33])([CH3:32])[CH:28]([CH2:27][CH:26]2[C:34]([N:10]2[C:5]3[CH:4]=[CH:3][CH:2]=[CH:24][C:6]=3[C:7]([C:16]#[C:17][C:18]3[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=3)([C:12]([F:14])([F:15])[F:13])[O:8][C:9]2=[O:11])=[O:35])[CH2:29]1

Participants

6

Reactant 4

HCID 6344DichloromethaneHCID 8471TriethylamineHCID 4771206-chloro-4-(2-phenylethynyl)-4-(trifluoromethyl)-1H-3,1-benzoxazin-2-oneHCID 534427834,7,7-Trimethyl-3-bicyclo[2.2.1]heptanecarbonyl chloride

Product 1

HCID 702711876-chloro-(1S)-camphanoyl-4-phenylethynyl-4-trifluoromethyl-1,4-dihydro-2H-3,1-benzoxazin-2-one

Reagents, catalysts & solvents 1

HCID 142844-(Dimethylamino)pyridineCatalyst

Procedure

To a solution containing (±) 6-chloro-4-phenylethynyl-4-trifluoromethyl-1,4-dihydro-2H-3,1-benzoxazin-2-one (2.24 g, 6.37 mmol), 4-dimethylaminopyridine (0.10 g, 0.8 mmol), and (-) camphanic acid chloride (2.07 g, 9.55 mmol) in 60 mL of dry dichloromethane, stirred under argon in an ice bath, was added triethylamine (2.22 mL, 15.9 mmol). The cooling bath was removed and the reaction was allowed to proceed at room temperature. When the reaction was complete by thin layer chromatography (SiO2, 4% EtOAc in CHCl3), the solution was diluted with 200 mL of CHCl3 and washed twice with 10% citric acid, then with brine. Upon drying (MgSO4) the solvent was removed on a rotary evaporator and the foamy reside was subjected to flash chromatography, eluting with CHCl3. There was obtained 575 mg of diastereomer I of 6-chloro-(1S)-camphanoyl-4-phenylethynyl-4-trifluoromethyl-1,4-dihydro-2H-3,1-benzoxazin-2-one as an oil, 1H-NMR (CDCl3): δ0.85 (s, 3H), 1.08 (s, 3H), 1.22 (s, 3H), 1.73-1.85 (m, 1H), 1.92-2.08 (m, 1H), 2.50-2.67 (m, 2H), 7.30-7.79 (m, 8H). This was followed by 1.52 g of mixed fractions (diastereomers I and II). Continued elution afforded 680 mg of the slower-moving diastereomer (II) of the title compound which, upon trituration with an ether/hexane mixture, gave clumps of white needles, mp 177°-178.5° C.; 1H-NMR (CDCl3): δ0.83 (s, 3H), 1.12 (s, 3H), 1.23 (s, 3H), 1.73-1.86 (m, 1H), 1.93-2.06 (m, 1H), 2.50-2.63 (m, 2H), 7.38-7.51 (m, 4H), 7.49-7.62 (m, 2H), 7.72 (d, J=9 Hz, 1H), 7.76 (d, J=2 Hz, 1 H).

Workup

  1. customThe cooling bath was removed
  2. customto proceed at room temperature
  3. additionthe solution was diluted with 200 mL of CHCl3
  4. washwashed twice with 10% citric acid
  5. dry with materialUpon drying (MgSO4) the solvent
  6. customwas removed on a rotary evaporator
  7. washeluting with CHCl3

Sources & evidence

ORD record
ord-0232e8695ffa4259829864f77bf583e7
Source dataset
uspto-grants-1996_05
Patent number
US05519021

Reaction notes

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