Methanol → HCID 59375101, compound

HRID 1811109Notes

Reaction equation

HRID 1811109 reaction equation
[C:1]([C:4]1[CH:5]=[CH:6][C:7]([C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=2[F:28])=[C:8]2[C:16]=1[NH:15][C:14]1[CH:13]=[C:12]([C:17](OCC)=[O:18])[CH:11]=[CH:10][C:9]2=1)(=[O:3])[NH2:2].[H-].[Al+3].[Li+].[H-].[H-].[H-].CO.C(O)(C(F)(F)F)=O>C1COCC1.CCOC(C)=O>[F:28][C:23]1[CH:24]=[CH:25][CH:26]=[CH:27][C:22]=1[C:7]1[C:8]2[C:9]3[C:14](=[CH:13][C:12]([CH2:17][OH:18])=[CH:11][CH:10]=3)[NH:15][C:16]=2[C:4]([C:1]([NH2:2])=[O:3])=[CH:5][CH:6]=1

Participants

7

Reactant 4

HCID 887MethanolHCID 6422Trifluoroacetic acidHCID 21226445Aluminium lithium hydride2×HCID 59375158HCID 59375158, compound

Product 1

HCID 59375101HCID 59375101, compoundYield 108.4%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of ethyl 8-carbamoyl-5-(2-fluorophenyl)-9H-carbazole-2-carboxylate (Example 3-12, 0.81 g, 2.152 mmol) in THF (26.9 mL) at 0° C. was treated with lithium aluminum hydride (1.0 M in THF, 3.01 mL, 3.01 mmol), and the mixture was stirred at rt for 5 h. Additional lithium aluminum hydride (1.3 mL, 1.3 mmol) was added and the mixture was stirred at rt overnight. The mixture was treated with methanol and TFA and diluted with EtOAc, washed with brine, dried and concentrated to provide impure 4-(2-fluorophenyl)-7-(hydroxymethyl)-9H-carbazole-1-carboxamide (0.78 g) contaminated with starting material. A small amount was purified by preparative HPLC to provide 4-(2-fluorophenyl)-7-(hydroxymethyl)-9H-carbazole-1-carboxamide, isolated as the TFA salt. 1H NMR (500 MHz, methanol-d4) δ 7.82 (1 H, d, J=7.8 Hz), 7.51 (1 H, s), 7.44-7.50 (1 H, m), 7.42 (1 H, td, J=7.5, 1.9 Hz), 7.25-7.30 (1 H, m), 7.22 (1 H, t, J=9.2 Hz), 7.05 (1 H, d, J=8.3 Hz), 6.99 (1 H, d, J=7.8 Hz), 6.85 (1 H, dd, J=8.0, 1.4 Hz), 4.62 (2 H, s). Mass spectrum m/z 334.9 (M+H)+.

Workup

  1. stirringthe mixture was stirred at rt overnight
  2. washwashed with brine
  3. customdried
  4. concentrationconcentrated

Sources & evidence

ORD record
ord-62344ff2912841d6ba277099a7f12f8e
Source dataset
uspto-grants-2013_01
Patent number
US08362065B2

Reaction notes

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