Sodium borohydride → benzyl 4-((1R,2S)-2-{2-[(5-amino-3-methylpyridin-2-yl)oxy]ethyl}cyclopropyl)piperidine-1-carboxylate

HRID 1850739Notes

Reaction equation

HRID 1850739 reaction equation
[BH4-].[Na+].[CH3:3][C:4]1[C:5]([O:13][CH2:14][CH2:15][C@@H:16]2[CH2:18][C@@H:17]2[CH:19]2[CH2:24][CH2:23][N:22]([C:25]([O:27][CH2:28][C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=3)=[O:26])[CH2:21][CH2:20]2)=[N:6][CH:7]=[C:8]([N+:10]([O-])=O)[CH:9]=1>CO.C(Cl)Cl.Cl[Ni]Cl>[NH2:10][C:8]1[CH:9]=[C:4]([CH3:3])[C:5]([O:13][CH2:14][CH2:15][C@@H:16]2[CH2:18][C@@H:17]2[CH:19]2[CH2:24][CH2:23][N:22]([C:25]([O:27][CH2:28][C:29]3[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=3)=[O:26])[CH2:21][CH2:20]2)=[N:6][CH:7]=1

Participants

6

Reactant 2

HCID 4311764Sodium borohydride2×HCID 70819067Benzyl 4-((1R,2S)-2-{2-[(3-methyl-5-nitropyridin-2-yl)oxy]ethyl}cyclopropyl)piperidine-1-carboxylate

Product 1

HCID 70856037benzyl 4-((1R,2S)-2-{2-[(5-amino-3-methylpyridin-2-yl)oxy]ethyl}cyclopropyl)piperidine-1-carboxylate

Reagents, catalysts & solvents 3

HCID 24385Nickel DichlorideCatalystHCID 887MethanolSolventHCID 6344DichloromethaneSolvent2×

Procedure

To the solution of NiCl2 (Nickel (II) Chloride-hexahydrate) in 12 ml of methanol was added 50 mg of NaBH4 (solution turned dark) at room temperature and the resulting mixture was stirred for 5 minutes. Benzyl 4-((1R,2S)-2-{2-[(3-methyl-5-nitropyridin-2-yl)oxy]ethyl}cyclopropyl)piperidine-1-carboxylate (from Step A; 550 mg, 1.25 mmol) in 5 ml of DCM was then added followed by the addition of 116 mg of NaBH4 in 3 portions. The mixture was then stirred for 20 minutes and then diluted with DCM and filtered through a pad of sodium sulfate (messy). The solution was concentrated to dryness under reduced pressure and taken up in 15 mL DCM. This material was then filtered through a pad of silica gel (extracting with ethyl acetate) and the filtrate was then washed by saturated aq. NaHCO3. The organics were then dried over sodium sulfate, filtered, and concentrated to dryness under reduced pressure to afford the title compound as a crude product which was used for next step. MS (ESI) m/z 410 [M+H]+.

Workup

  1. stirringThe mixture was then stirred for 20 minutes
  2. filtrationfiltered through a pad of sodium sulfate (messy)
  3. concentrationThe solution was concentrated to dryness under reduced pressure
  4. filtrationThis material was then filtered through a pad of silica gel (extracting with ethyl acetate)
  5. washthe filtrate was then washed by saturated aq. NaHCO3
  6. dry with materialThe organics were then dried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated to dryness under reduced pressure

Sources & evidence

ORD record
ord-42174004ddd24f2e816f33a4b92d489d
Source dataset
uspto-grants-2015_02
Patent number
US08957062B2

Reaction notes

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