Hydrochloric Acid → tert-Butyl 4-(methylamino)piperidine-1-carboxylate

HRID 2395783Notes

Reaction equation

HRID 2395783 reaction equation
Cl.CN.[OH-].[K+].[CH3:6][C:7]([CH3:19])([O:9][C:10]([N:12]1[CH2:17][CH2:16][C:15](=O)[CH2:14][CH2:13]1)=[O:11])[CH3:8].[C:20]([BH3-])#[N:21].[Na+].Cl>CO>[CH3:6][C:7]([CH3:19])([O:9][C:10]([N:12]1[CH2:17][CH2:16][CH:15]([NH:21][CH3:20])[CH2:14][CH2:13]1)=[O:11])[CH3:8]

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 14797Potassium Hydroxide2×HCID 735900tert-Butyl 4-oxopiperidine-1-carboxylateHCID 5003444Sodium cyanoborohydrideHCID 6364545Methylamine hydrochloride

Product 1

HCID 15380702tert-Butyl 4-(methylamino)piperidine-1-carboxylate

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent2×

Procedure

Methylamine hydrochloride (2.36 g) is dissolved in methanol (50 ml) and potassium hydroxide pellets (0.60 g) and N-(1,1-di-methylethoxycarbonyl)-4-piperidone are added. Sodium cyanoborohydride (0.69 g) in methanol (5 ml) is added and the mixture is stirred 2 hrs. Potassium hydroxide pellets (1.96 g) are added to the mixture which is stirred 1 hr and acidified to pH 2 with 6M hydrochloric acid and concentrated. The mixture is diluted with water (50 ml) and extracted with ether (3×80 ml) which is discarded. The aqueous layer is basified to pH 11 with potassium hydroxide pellets, saturated with sodium chloride and extracted with ether (6×80 ml). The combined organic extracts are dried with magnesium sulfate and concentrated to afford an oil which is chromatographed on silica gel with a methanol/chloroform gradient (5-30%). Fractions are pooled on the basis of TLC (Rf =0.13, 20% methanol/chloroform) to give the title compound, NMR (CDCl3) 4.04, 2.79, 2.54, 2.46, 2.33, 1.88, 1.46, and 1.26 δ.

Workup

  1. stirringis stirred 1 hr
  2. concentrationconcentrated
  3. additionThe mixture is diluted with water (50 ml)
  4. extractionextracted with ether (3×80 ml) which
  5. extractionextracted with ether (6×80 ml)
  6. dry with materialThe combined organic extracts are dried with magnesium sulfate
  7. concentrationconcentrated
  8. customto afford an oil which
  9. customis chromatographed on silica gel with a methanol/chloroform gradient (5-30%)

Sources & evidence

ORD record
ord-09aa6149bf514666b2da17dff61800fd
Source dataset
uspto-grants-1996_02
Patent number
US05489593

Reaction notes

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