Formic Acid → (r)-Cyclopropanecarboxylic acid[9-(3-fluorobenzyl)-6-formyl-2,3,4,9-tetrahydro-1h-carbazol-3-yl]-amide

HRID 545579Notes

Reaction equation

HRID 545579 reaction equation
[C:1]([C:3]1[CH:4]=[C:5]2[C:13](=[CH:14][CH:15]=1)[N:12]([CH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[C:19]([F:23])[CH:18]=1)[C:11]1[CH2:10][CH2:9][C@@H:8]([NH:24][C:25]([CH:27]3[CH2:29][CH2:28]3)=[O:26])[CH2:7][C:6]2=1)#N.C(O)=[O:31]>[Al].[Ni].CO>[F:23][C:19]1[CH:18]=[C:17]([CH:22]=[CH:21][CH:20]=1)[CH2:16][N:12]1[C:11]2[CH2:10][CH2:9][C@@H:8]([NH:24][C:25]([CH:27]3[CH2:29][CH2:28]3)=[O:26])[CH2:7][C:6]=2[C:5]2[C:13]1=[CH:14][CH:15]=[C:3]([CH:1]=[O:31])[CH:4]=2

Participants

5

Reactant 2

HCID 284Formic AcidHCID 59161284(r)-Cyclopropanecarboxylic acid[6-cyano-9-(3-fluorobenzyl)-2,3,4,9-tetrahydro-1h-carbazol-3-yl]amide

Product 1

HCID 59161221(r)-Cyclopropanecarboxylic acid[9-(3-fluorobenzyl)-6-formyl-2,3,4,9-tetrahydro-1h-carbazol-3-yl]-amideYield 95%

Reagents, catalysts & solvents 2

HCID 6336846Nickel aluminideCatalystHCID 887MethanolSolvent

Procedure

Combine (R)-cyclopropanecarboxylic acid[6-cyano-9-(3-fluorobenzyl)-2,3,4,9-tetrahydro-1H-carbazol-3-yl]amide (Example 194) (3.70 g, 9.55 mmol) and nickel-aluminum catalyst (10.0 g) in 90% formic acid and heat at 90-100° C. for 18 h. Dilute with methanol, filter to remove catalyst, and concentrate the filtrate in vacuo. Neutralize the filtrate by addition of solid NaHCO3 after taking up in ethyl acetate/water. Dry the ethyl acetate portion over Na2SO4, filter, and evaporate to give 3.53 g (95%) of the title compound as a foam. MS (ES): n/z 391 (M+1); 1H NMR(DMSO-d6): δ 9.90 (s, 1H), 8.19 (d, 1H), 8.04 (s, 1H), 7.61 (d, 1H), 7.57 (d, 1H), 7.37 (dd, 1H), 7.15 (m, 1H), 6.81-6.92 (m, 2H), 5.44 (s, 2H), 4.08 (m, 1H), 3.03 (dd, 1H), 2.57-2.82 (m, 4H), 2.00 (m, 1H), 1.82 (m, 1H), 1.59 (m, 1H), 0.65 (m, 4H).

Workup

  1. filtrationfilter
  2. customto remove catalyst
  3. concentrationconcentrate the filtrate in vacuo
  4. additionNeutralize the filtrate by addition of solid NaHCO3
  5. dry with materialDry the ethyl acetate portion over Na2SO4
  6. filtrationfilter
  7. customevaporate

Sources & evidence

ORD record
ord-ecd5a5bd671d401db6bc873c456cf590
Source dataset
uspto-grants-2011_05
Patent number
US07935722B2

Reaction notes

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