Ammonium Chloride → tert-Butyl ((3R,4R,5S)-1-(3-amino-5-methylpyridin-4-yl)-4-{[tert-butyl(dimethyl) silyl]oxy}-5-methylpiperidin-3-yl)carbamate

HRID 924435Notes

Reaction equation

HRID 924435 reaction equation
[Si:1]([O:8][C@@H:9]1[C@@H:14]([CH3:15])[CH2:13][N:12]([C:16]2[C:21]([N+:22]([O-])=O)=[CH:20][N:19]=[CH:18][C:17]=2[CH3:25])[CH2:11][C@H:10]1[NH:26][C:27](=[O:33])[O:28][C:29]([CH3:32])([CH3:31])[CH3:30])([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[Cl-].[NH4+]>CCO.O.[Fe]>[NH2:22][C:21]1[CH:20]=[N:19][CH:18]=[C:17]([CH3:25])[C:16]=1[N:12]1[CH2:13][C@H:14]([CH3:15])[C@@H:9]([O:8][Si:1]([C:4]([CH3:7])([CH3:5])[CH3:6])([CH3:2])[CH3:3])[C@H:10]([NH:26][C:27](=[O:33])[O:28][C:29]([CH3:32])([CH3:31])[CH3:30])[CH2:11]1

Participants

6

Reactant 2

HCID 25517Ammonium Chloride2×HCID 86726885tert-Butyl [(3R,4R,5S)-4-{[tert-butyl(dimethyl)silyl]oxy}-5-methyl-1-(3-methyl-5-nitropyridin-4-yl)piperidin-3-yl]carbamate

Product 1

HCID 86726886tert-Butyl ((3R,4R,5S)-1-(3-amino-5-methylpyridin-4-yl)-4-{[tert-butyl(dimethyl) silyl]oxy}-5-methylpiperidin-3-yl)carbamateYield 100%

Reagents, catalysts & solvents 3

HCID 23925IronCatalyst2×HCID 702EthanolSolvent2×HCID 962WaterSolvent

Procedure

A mixture of tert-butyl [(3R,4R,5S)-4-{[tert-butyl(dimethyl)silyl]oxy}-5-methyl-1-(3-methyl-5-nitropyridin-4-yl)piperidin-3-yl]carbamate (12 mg, 0.025 mmol), iron powder (38 mg, 0.68 mmol) and ammonium chloride (55 mg, 1.0 mmol) in EtOH (0.9 mL) and water (0.2 mL) was stirred at room temperature for 16 h. A second aliquot of iron powder (380 mg), ammonium chloride (550 mg), and EtOH (1 mL) were added and stirring was continued at 55° C. for 3 h. The crude reaction mixture was filtered through a pad of diatomaceous earth and the inorganics were washed thoroughly with EtOAc. The filtrate was concentrated under reduced pressure to give the sub-title compound (11 mg, 100%), which was used directly in the subsequent reaction without further purification. LCMS (ESI) calc. for C23H43N4O3Si [M+H]+: m/z=451.3. found 451.2.

Workup

  1. stirringstirring
  2. waitwas continued at 55° C. for 3 h
  3. customThe crude reaction mixture
  4. filtrationwas filtered through a pad of diatomaceous earth
  5. washthe inorganics were washed thoroughly with EtOAc
  6. concentrationThe filtrate was concentrated under reduced pressure

Sources & evidence

ORD record
ord-94bb32d0631f4c7f95a585ec3b7faa68
Source dataset
uspto-grants-2016_03
Patent number
US09278950B2

Reaction notes

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