Dimethylformamide → HCID 86597103, compound

HRID 1297273Notes

Reaction equation

HRID 1297273 reaction equation
P(Cl)(Cl)(Cl)=O.[CH2:6]([O:13][C:14]1[CH:19]=[CH:18][C:17]([N:20]2[C:28]3[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=3)[CH:22]=[C:21]2[CH3:29])=[CH:16][C:15]=1[F:30])[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1.[OH-].[Na+].CN(C)[CH:35]=[O:36]>>[CH2:6]([O:13][C:14]1[CH:19]=[CH:18][C:17]([N:20]2[C:28]3[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=3)[C:22]([CH:35]=[O:36])=[C:21]2[CH3:29])=[CH:16][C:15]=1[F:30])[C:7]1[CH:8]=[CH:9][CH:10]=[CH:11][CH:12]=1

Participants

5

Reactant 4

HCID 6228Dimethylformamide2×HCID 14798Sodium HydroxideHCID 24813Phosphorus oxychlorideHCID 69300406HCID 69300406, compound

Product 1

HCID 86597103HCID 86597103, compound

Procedure

Phosphorous oxychloride (3 mL) was added to anhydrous dimethylformamide (6 mL) and the mixture allowed to stir at room temperature for 15 min. A mixture of 1-(4-benzyloxy-3-fluorophenyl)-2-methyl-1H-indole (1.03 g, 3.1 mmol) in dimethylformamide (10 mL) was added and the mixture heated to 80° C. and held for 18 hr. The reaction mixture was poured onto ice and adjusted to a pH of 7 by the addition of 2 N NaOH. The mixture was extracted with ethyl acetate (2×100 mL), the organic layer washed with water and brine and dried over MgSO4, and evaporated to provide the product as a dark solid. Purification by silica gel chromatography (25% EtOAC-hexanes) provided a white solid (0.84 gr, 76%): mp 166-168-152° C.; 1H NMR (DMSO-d6): δ 2.55 (3H, s), 5.30 (2H, s), 7.04 (1H, d, J=6.9 Hz), 7.19-7.28 (2H, m), 7.23-7.52 (7H, m), 7.44 (2H, dd, J=6.0 Hz, J=1.4 Hz), 7.59 (1H, dd, J=11.7 Hz, J=2.5), 8.17 (1H, dd, J=7.0 Hz, J=1.0), 10.20 (1H, s) Hz; MS m/z (M+H)+ 360: Anal. for C23H18FNO2 (0.1H2O): Calc'd: C, 76.48; H, 5.08; N, 3.88. Found: C, 76.39; H, 4.81; N, 3.69

Workup

  1. additionwas added
  2. temperaturethe mixture heated to 80° C.
  3. waitheld for 18 hr
  4. additionThe reaction mixture was poured onto ice
  5. extractionThe mixture was extracted with ethyl acetate (2×100 mL)
  6. washthe organic layer washed with water and brine
  7. dry with materialdried over MgSO4
  8. customevaporated

Sources & evidence

ORD record
ord-97c0404ef1c141acbdb8951cbffff1cf
Source dataset
uspto-grants-2007_07
Patent number
US07250440B2

Reaction notes

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