Ammonium Hydroxide → 4'-Fluoro-biphenyl-4-carboxylic acid (6-aminomethyl-1,2,3,4-tetrahydro-naphthalen-2-yl)-amide

HRID 968653Notes

Reaction equation

HRID 968653 reaction equation
[C:1]([C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[CH2:9][CH:8]([NH:13][C:14]([C:16]1[CH:21]=[CH:20][C:19]([C:22]3[CH:27]=[CH:26][C:25]([F:28])=[CH:24][CH:23]=3)=[CH:18][CH:17]=1)=[O:15])[CH2:7][CH2:6]2)#[N:2].[NH4+].[OH-]>CN(C=O)C.[Ni]>[NH2:2][CH2:1][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[CH2:9][CH:8]([NH:13][C:14]([C:16]1[CH:21]=[CH:20][C:19]([C:22]3[CH:23]=[CH:24][C:25]([F:28])=[CH:26][CH:27]=3)=[CH:18][CH:17]=1)=[O:15])[CH2:7][CH2:6]2

Participants

5

Reactant 2

HCID 14923Ammonium HydroxideHCID 59016074HCID 59016074, compound

Product 1

HCID 113947174'-Fluoro-biphenyl-4-carboxylic acid (6-aminomethyl-1,2,3,4-tetrahydro-naphthalen-2-yl)-amideYield 94%

Reagents, catalysts & solvents 2

HCID 935NickelCatalystHCID 6228DimethylformamideSolvent

Procedure

A suspension of 4′-fluoro-biphenyl-4-carboxylic acid (6-cyano-1,2,3,4-tetrahydro-naphthalen-2-yl)-amide, 3, (1.430 g, 3.514 mmol), Raney-Ni (0.5 g) and 28% NH4OH (1.0 mL) in DMF (25 mL) is hydrogenated for 18 hours. The catalyst is removed by filtration and the filtrate concentrated in vacuo to afford 1.352 g (94% yield) of the desired product. 1H NMR (300 MHz, DMF-D7) δ 8.55 (d, J=7.5 Hz, 1H), 8.20 (d, J=8.7 Hz, 2H), 7.72-7.85 (m, 4H), 7.35 (t, J=9.3 Hz, 2H), 6.95-7.23 (br, 3H), 4.20-4.42 (m, 1H), 3.12-3.24 (br, 2H), 2.90-3.08 (m, 4H), 2.11-2.25 (m, 1H), 1.90 (m, 1H); 13C NMR (75 MHz, DMF-D7) δ166.2, 164.8, 142.6, 136.8, 135.8, 134.5, 133.8, 129.6, 129.4, 129.3, 128.5, 127.0, 125.6, 116.4, 116.1, 64.0, 46.9, 34.2, 28.7, 28.0; 19F NMR (282 MHz, DMF-D7) δ 46.6; LRMS: 375.3 (M+H), 358.3 (M+H−NH3), HRMS: calcd: for C24H24FN2O 375.1873, found: 375.1866.

Workup

  1. customThe catalyst is removed by filtration
  2. concentrationthe filtrate concentrated in vacuo

Sources & evidence

ORD record
ord-5c8d54a2fa974a97af0f1a3cefa36adc
Source dataset
uspto-grants-2007_12
Patent number
US07304065B2

Reaction notes

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