Ammonium Chloride → tert-Butyl 4-carbamoyl-4-methylpiperidine-1-carboxylate

HRID 1622308Notes

Reaction equation

HRID 1622308 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C:11]([CH3:17])([C:14](O)=[O:15])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].CC[N:20](C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[NH4+].[Cl-]>CN(C=O)C>[C:14]([C:11]1([CH3:17])[CH2:12][CH2:13][N:8]([C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:7])[CH2:9][CH2:10]1)(=[O:15])[NH2:20]

Participants

6

Reactant 4

HCID 25517Ammonium ChlorideHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 232828481-[(Tert-butoxy)carbonyl]-4-methylpiperidine-4-carboxylic acid

Product 1

HCID 53393793tert-Butyl 4-carbamoyl-4-methylpiperidine-1-carboxylateYield 80.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of 1-(tert-butoxycarbonyl)-4-methylpiperidine-4-carboxylic acid (1.00 g, 4.00 mmol) in DMF (41 mL) and DIPEA (2.9 mL, 17 mmol) was treated with HATU (2.4 g, 6.3 mmol). The solution was stirred for 20 minutes and NH4Cl (0.450 g, 8.40 mmol) was added. The mixture was stirred overnight and then evaporated to dryness. The residue was partitioned between EtOAc (100 mL) and water (150 mL). The phases were separated and the aqueous phase was extracted with EtOAc. The combined organic phases were washed with HCl (1.0 N solution in water), saturated aqueous NaHCO3 solution, water and brine; dried over Na2SO4; filtered and concentrated. The residue was purified by column chromatography (SiO2, 10% MeOH in DCM) to give tert-butyl 4-carbamoyl-4-methylpiperidine-1-carboxylate (781 mg, 78%). LC-MS: (FA) ES+ 265 (M+Na).

Workup

  1. stirringThe mixture was stirred overnight
  2. customevaporated to dryness
  3. customThe residue was partitioned between EtOAc (100 mL) and water (150 mL)
  4. customThe phases were separated
  5. extractionthe aqueous phase was extracted with EtOAc
  6. washThe combined organic phases were washed with HCl (1.0 N solution in water), saturated aqueous NaHCO3 solution, water and brine
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe residue was purified by column chromatography (SiO2, 10% MeOH in DCM)

Sources & evidence

ORD record
ord-ea88b66707da44cdbe14a9df0a10660a
Source dataset
uspto-grants-2014_07
Patent number
US08778931B2

Reaction notes

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