Acetic Acid → tert-Butyl cis(+/-)-4-{[(benzyloxy)carbonyl]amino}-3-(dimethylamino)piperidine-1-carboxylate

HRID 1425308Notes

Reaction equation

HRID 1425308 reaction equation
C=O.[C:3](O)(=O)C.[C:7]([BH3-])#[N:8].[Na+].N[C@H:12]1[C@@H:17]([NH:18][C:19]([O:21][CH2:22][C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)=[O:20])[CH2:16][CH2:15][N:14]([C:29]([O:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:30])[CH2:13]1>O1CCCC1.CO>[CH2:22]([O:21][C:19]([NH:18][C@H:17]1[CH2:16][CH2:15][N:14]([C:29]([O:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:30])[CH2:13][C@H:12]1[N:8]([CH3:7])[CH3:3])=[O:20])[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 712FormaldehydeHCID 5003444Sodium cyanoborohydrideHCID 69440349tert-Butyl (3R,4S)-3-amino-4-{[(benzyloxy)carbonyl]amino}piperidine-1-carboxylate

Product 1

HCID 86648775tert-Butyl cis(+/-)-4-{[(benzyloxy)carbonyl]amino}-3-(dimethylamino)piperidine-1-carboxylateYield 94%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

A 37% aqueous formaldehyde solution (346 μL, 4.26 mmol), acetic acid (110 μL, 1.92 mmol) and sodium cyanoborohydride (67 mg, 1.07 mmol) were added to a mixed solution of tert-butyl cis(±)-3-amino-4-{[(benzyloxy)carbonyl]amino}piperidine-1-carboxylate obtained in Example (200a) (149 mg, 0.43 mmol) in tetrahydrofuran (2 mL) and methanol (2 mL) under ice-cooling, and the mixture was stirred at room temperature for two hours. The reaction solution was concentrated under reduced pressure, and aqueous saturated sodium bicarbonate solution was added to the residue, followed by extraction with chloroform. The resulting organic layer was dried over anhydrous sodium sulfate, and then the insoluble matter was separated by filtration. The filtrate was concentrated under reduced pressure, and the resulting residue was purified by silica gel column chromatography (eluent: chloroform:methanol=10:1 v/v) to obtain 152 mg of the title compound (94%) as a colorless oily substance.

Workup

  1. temperaturecooling
  2. concentrationThe reaction solution was concentrated under reduced pressure, and aqueous saturated sodium bicarbonate solution
  3. additionwas added to the residue
  4. extractionfollowed by extraction with chloroform
  5. dry with materialThe resulting organic layer was dried over anhydrous sodium sulfate
  6. customthe insoluble matter was separated by filtration
  7. concentrationThe filtrate was concentrated under reduced pressure
  8. customthe resulting residue was purified by silica gel column chromatography (eluent: chloroform:methanol=10:1 v/v)

Sources & evidence

ORD record
ord-f1edab8d9a50492db549aa4814255088
Source dataset
uspto-grants-2015_01
Patent number
US08927588B2

Reaction notes

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