Sodium borohydride → Tert-butyl 4-(5-amino-3-chloropyridin-2-yl)piperazine-1-carboxylate

HRID 1993639Notes

Reaction equation

HRID 1993639 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[C:19]([Cl:20])=[CH:18][C:17]([N+:21]([O-])=O)=[CH:16][N:15]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[BH4-].[Na+]>CO.O.O.O.O.O.O.[Ni](Cl)Cl>[C:1]([O:5][C:6]([N:8]1[CH2:9][CH2:10][N:11]([C:14]2[C:19]([Cl:20])=[CH:18][C:17]([NH2:21])=[CH:16][N:15]=2)[CH2:12][CH2:13]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 2

HCID 4311764Sodium borohydrideHCID 685401434-(3-Chloro-5-nitro-pyridin-2-yl)-piperazine-1-carboxylic acid tert-butyl ester

Product 1

HCID 68536999Tert-butyl 4-(5-amino-3-chloropyridin-2-yl)piperazine-1-carboxylateYield 63%

Reagents, catalysts & solvents 2

HCID 11791229Dichloronickel;hexahydrateCatalystHCID 887MethanolSolvent

Procedure

Place 4-(3-chloro-5-nitro-pyridin-2-yl)-piperazine-1-carboxylic acid tert-butyl ester (3.09 g, 9.01 mmol) in methanol (50 mL). Add nickel(II) chloride hexahydrate (10.7 g, 45.1 mmol) and cool the reaction to 0° C. Add sodium borohydride (5.11 g, 135.15 mmol) in portions and stir at 0° C. for 2 hours. Add CH2Cl2 and filter through a pad of Celite®. Wash filter cake with CH2Cl2 and collect filtrate. Add saturated aq. sodium bicarbonate solution to the filtrate and separate organic layer. Extract aqueous layer with CH2Cl2 (2×30 mL). Combine organic extracts, dry over Mg2SO4, filter, and concentrate under reduced pressure. Subject residue to silica gel chromatography eluting with 0-70% EtOAc:hexane to yield 1.77 g (63%) of the title compound. MS(ES): m/z=311.2 [M−H].

Workup

  1. customthe reaction to 0° C
  2. filtrationAdd CH2Cl2 and filter through a pad of Celite®
  3. washWash
  4. filtrationfilter cake with CH2Cl2
  5. customcollect filtrate
  6. customAdd saturated aq. sodium bicarbonate solution to the filtrate and separate organic layer
  7. dry with materialCombine organic extracts, dry over Mg2SO4
  8. filtrationfilter
  9. concentrationconcentrate under reduced pressure
  10. washSubject residue to silica gel chromatography eluting with 0-70% EtOAc

Sources & evidence

ORD record
ord-d2be7081b1ed4ac6a4f0055fc8c1dba2
Source dataset
uspto-grants-2010_01
Patent number
US07652015B2

Reaction notes

Loading…