Sodium borohydride → 4-[1-(2-Amino-ethyl)-4-(3-chloro-4-fluoro-phenyl)-1H-imidazol-2-yl]-piperidine-1-carboxylic acid tert-butyl ester

HRID 1685160Notes

Reaction equation

HRID 1685160 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([C:14]2[N:15]([CH2:27][C:28]#[N:29])[CH:16]=[C:17]([C:19]3[CH:24]=[CH:23][C:22]([F:25])=[C:21]([Cl:26])[CH:20]=3)[N:18]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[BH4-].[Na+]>CO.[Ni](Cl)Cl>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([C:14]2[N:15]([CH2:27][CH2:28][NH2:29])[CH:16]=[C:17]([C:19]3[CH:24]=[CH:23][C:22]([F:25])=[C:21]([Cl:26])[CH:20]=3)[N:18]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

5

Reactant 2

HCID 4311764Sodium borohydrideHCID 672655344-[4-(3-Chloro-4-fluoro-phenyl)-1-cyanomethyl-1H-imidazol-2-yl]-piperidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 672651144-[1-(2-Amino-ethyl)-4-(3-chloro-4-fluoro-phenyl)-1H-imidazol-2-yl]-piperidine-1-carboxylic acid tert-butyl esterYield 125.3%

Reagents, catalysts & solvents 2

HCID 24385Nickel DichlorideCatalystHCID 887MethanolSolvent

Procedure

Dissolve 4-[4-(3-chloro-4-fluoro-phenyl)-1-cyanomethyl-1H-imidazol-2-yl]-piperidine-1-carboxylic acid tert-butyl ester (0.94 mmol; 392.9 mg) in methanol (20 mL). Add nickel dichloride (1.03 mmol; 135 mg). Add sodium tetrahydroborate (18.8 mmol; 717 mg) portion-wise. Evaporate and partition between water/DCM and stir 20 min. Add Celite®, stir 30 min and filter. Rinse solids with DCM, 10% MeOH/DCM. Add 2 mL 2M NH3-MeOH to organic layer and evaporate. Dissolve the residue in DCM, wash with brine, dry over MgSO4, filter through Celite® and evaporate to provide the title compound (498 mg; 125%). MS (ES): m/z=423 (M+H).

Workup

  1. customEvaporate
  2. custompartition between water/DCM
  3. stirringAdd Celite®, stir 30 min
  4. filtrationfilter
  5. washRinse solids with DCM, 10% MeOH/DCM
  6. additionAdd 2 mL 2M NH3-MeOH to organic layer
  7. customevaporate
  8. dissolutionDissolve the residue in DCM
  9. washwash with brine
  10. dry with materialdry over MgSO4
  11. filtrationfilter through Celite®
  12. customevaporate

Sources & evidence

ORD record
ord-86207bdedc1042bfa45d0a56c977e885
Source dataset
uspto-grants-2012_04
Patent number
US08148387B2

Reaction notes

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