Phosphorus trichloride → HCID 86593818, compound

HRID 1375726Notes

Reaction equation

HRID 1375726 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([O:25][CH3:26])=[C:6]([C@@:8]2([F:24])[C:16]3[C:11](=[CH:12][C:13]([C:17]([F:20])([F:19])[F:18])=[CH:14][CH:15]=3)[N:10]([CH2:21]O)[C:9]2=[O:23])[CH:7]=1.P(Cl)(Cl)[Cl:28]>C(Cl)Cl>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([O:25][CH3:26])=[C:6]([C@@:8]2([F:24])[C:16]3[C:11](=[CH:12][C:13]([C:17]([F:19])([F:20])[F:18])=[CH:14][CH:15]=3)[N:10]([CH2:21][Cl:28])[C:9]2=[O:23])[CH:7]=1

Participants

4

Reactant 2

HCID 24387Phosphorus trichlorideHCID 69331104HCID 69331104, compound

Product 1

HCID 86593818HCID 86593818, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of (S)-3-(5-chloro-2-methoxyphenyl)-1-(hydroxymethyl)-3-fluoro-6-(trifluoromethyl)indolin-2-one ((S)-VI) (64.5 g, 0.166 mol) in CH2Cl2 (700 mL) was added PCl3 (2.0 M in CH2Cl2, 255.0 mL, 0.510 mol) dropwise at 0° C. under N2 over a period of 50 min. The resultant mixture was warmed to rt. and the stirring continued overnight (16 h). The mixture was quenched with ice at 0° C. and the resultant mixture was stirred vigorously for 30 min. The organic layer was separated and the aqueous layer was washed with CH2Cl2. The combined organic layer was washed with brine and dried over Na2SO4. Chromatography (silica gel, EtOAc/Hexanes) provided the title compound as a white dry foam (42.0 g, 62% yield). LC/MS m/e: (no molecular ion), 97% purity. 1H NMR (CDCl3): δ 3.55 (s, 3H), 5.39 (d, J=10.5 Hz, 1H), 5.95 (d, J=11.0 Hz, 1H), 6.76 (dd, J=1.5, 9.0 Hz, 1H), 7.28 (m, 2H), 7.35 (dd, J=1.5, 9.0 Hz, 1H), 7.40 (d, J=8.0 Hz, 1H), 7.78 (dd, J=1.0, 2.5 Hz, 1H).

Workup

  1. customthe stirring continued overnight (16 h)
  2. customThe mixture was quenched with ice at 0° C.
  3. customThe organic layer was separated
  4. washthe aqueous layer was washed with CH2Cl2
  5. washThe combined organic layer was washed with brine
  6. dry with materialdried over Na2SO4

Sources & evidence

ORD record
ord-8d3dd353ec33434f9a32d45195bfb217
Source dataset
uspto-grants-2007_01
Patent number
US07169803B2

Reaction notes

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