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

HRID 968656Notes

Reaction equation

HRID 968656 reaction equation
[C:1]([C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[CH2:9][CH:8]([N:13]([CH3:29])[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]([N:13]([CH3:29])[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 590160724'-Fluoro-biphenyl-4-carboxylic acid (6-cyano-1,2,3,4-tetrahydro-naphthalen-2-yl)-methyl-amide

Product 1

HCID 114291644'-Fluoro-biphenyl-4-carboxylic acid (6-aminomethyl-1,2,3,4-tetrahydro-naphthalen-2-yl)-methyl-amide

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)-methyl-amide, 7, (0.200 g, 0.521 mmol), 28% NH4OH (2 mL) and Raney Ni (0.2 g) in DMF (5 mL) is stirred vigorously at room temperature under 1 atm of H2 for 18 hrs. The catalyst is removed by filtration and the filtrate is purified by directly loading to prep-HPLC column eluted with CH3CN—H2O (0.1% TFA) to afford 0.098 g of the desired product. 1H NMR (300 MHz, CD3OD) δ 7.42-7.78 (m, 6H), 7.03-7.16 (m, 5H), 4.83 (m, 1H), 3.91-4.07 (m, 3H), 2.60-3.31 (m, 6H), 2.01-2.20 (m, 2H); 13C NMR (75 MHz, CD3OD) δ 164.7, 161.4, 160.4, 141.7, 136.4, 135.5, 131.3, 130.0, 129.1, 128.8, 128.8, 127.0, 126.3, 115.7, 115.5, 56.0, 51.2, 42.9, 31.8, 29.0, 26.9; LRMS: 411.28 (M+Na), 388.27 (M+H), 372.25 (M+H−NH3).

Workup

  1. customThe catalyst is removed by filtration
  2. customthe filtrate is purified
  3. washeluted with CH3CN—H2O (0.1% TFA)

Sources & evidence

ORD record
ord-aa1ffdc948324c76a0d4b3aafccd2ac0
Source dataset
uspto-grants-2007_12
Patent number
US07304065B2

Reaction notes

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