Sodium borohydride → HCID 25174808, compound

HRID 2194900Notes

Reaction equation

HRID 2194900 reaction equation
[Cl:1][C:2]1[CH:42]=[C:41]([CH3:43])[CH:40]=[C:39]([Cl:44])[C:3]=1[O:4][CH2:5][CH2:6][O:7][C:8]1[CH:13]=[CH:12][C:11]([CH2:14][CH:15]([C:18]2[CH:19]=[N:20][C:21]([C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][C:29]=3[CH2:34][CH2:35][CH2:36][O:37][CH3:38])=[CH:22][C:23]=2[C:24]([F:27])([F:26])[F:25])[C:16]#[N:17])=[CH:10][CH:9]=1.[BH4-].[Na+]>CCO.N.[Ni](Cl)Cl>[Cl:1][C:2]1[CH:42]=[C:41]([CH3:43])[CH:40]=[C:39]([Cl:44])[C:3]=1[O:4][CH2:5][CH2:6][O:7][C:8]1[CH:9]=[CH:10][C:11]([CH2:14][CH:15]([C:18]2[CH:19]=[N:20][C:21]([C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][C:29]=3[CH2:34][CH2:35][CH2:36][O:37][CH3:38])=[CH:22][C:23]=2[C:24]([F:27])([F:26])[F:25])[CH2:16][NH2:17])=[CH:12][CH:13]=1

Participants

6

Reactant 2

HCID 4311764Sodium borohydrideHCID 67446828HCID 67446828, compound

Product 1

HCID 25174808HCID 25174808, compound

Reagents, catalysts & solvents 3

HCID 24385Nickel DichlorideCatalystHCID 222AmmoniaSolventHCID 702EthanolSolvent

Procedure

To a solution of 3-{4-[2-(2,6-dichloro-4-methylphenoxy)ethoxy]phenyl}-2-[6-[2-(3-methoxy propyl)phenyl]-4-(trifluoromethyl)pyridin-3-yl]propanenitrile from step 5 (1 eq.) in EtOH (0.05M) at 0° C. was added nickel chloride (NiCl2; 1 eq.) and then portionwise sodium borohydride (3 eq.). The final mixture was stirred for 2 h at room temperature, poured in conc. ammonia and extracted with EtOAc. The organic extract was washed with water, brine, dried over Na2SO4, filtered and concentrated. Purification by column chromatography on silica gel, eluting with EtOAc/MeOH(NH3 2M) 10%, afforded the title compound as a colorless oil. 1H NMR (500 MHz, CD3OD): δ 8.91 (s, 1H), 7.63 (s, 1H), 7.44-7.32 (m, 4H), 7.19 (s, 2H), 7.02 (d, 2H), 6.80 (d, 2H), 4.34-4.27 (m, 4H), 3.56-3.49 (m, 1H), 3.27-3.15 (m, 6H), 3.11 (d, 2H), 3.06-2.99 (m, 1H), 2.80-2.70 (m, 2H), 2.29 (s, 3H), 1.71-1.64 (m, 2H).

Workup

  1. extractionextracted with EtOAc
  2. extractionThe organic extract
  3. washwas washed with water, brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customPurification by column chromatography on silica gel
  8. washeluting with EtOAc/MeOH(NH3 2M) 10%

Sources & evidence

ORD record
ord-47e2d39b5551482fb7e962ea9ea84196
Source dataset
uspto-grants-2012_12
Patent number
US08334308B2

Reaction notes

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