Tert-butyl 4-hydroxypiperidine-1-carboxylate → 1,1-Dimethylethyl 4-[[(4-amino-5-chloro-2,3-dihydro-7-benzofuranyl)carbonyl]oxy]-1-piperidinecarboxylate

HRID 362785Notes

Reaction equation

HRID 362785 reaction equation
[OH:1][CH:2]1[CH2:7][CH2:6][N:5]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:4][CH2:3]1.[NH2:15][C:16]1[C:21]2[CH2:22][CH2:23][O:24][C:20]=2[C:19]([C:25](Cl)=[O:26])=[CH:18][C:17]=1[Cl:28]>CN(C)C1C=CN=CC=1.ClCCl>[NH2:15][C:16]1[C:21]2[CH2:22][CH2:23][O:24][C:20]=2[C:19]([C:25]([O:1][CH:2]2[CH2:3][CH2:4][N:5]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:6][CH2:7]2)=[O:26])=[CH:18][C:17]=1[Cl:28]

Participants

5

Reactant 2

HCID 643502Tert-butyl 4-hydroxypiperidine-1-carboxylateHCID 539800704-Amino-5-chloro-2,3-dihydro-7-benzofurancarbonyl chloride

Product 1

HCID 543178411,1-Dimethylethyl 4-[[(4-amino-5-chloro-2,3-dihydro-7-benzofuranyl)carbonyl]oxy]-1-piperidinecarboxylateYield 59.3%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent2×

Procedure

A solution of 1,1-dimethylethyl 4-hydroxy-1-piperidinecarboxylate (4.02 g) and N,N-dimethyl-4-pyridinamine (3.7 g) in dichloromethane (200 ml) was stirred at room temperature. A solution of intermediate (7) (4.8 g) in CH2Cl2 (200 ml) was poured into the solution. The reaction mixture was stirred for 3 hours at room temperature. The mixture was washed with water, a 5% NaOH solution and again water. The organic layer was separated, dried over MgSO4, filtered and the solvent was evaporated. The residue (7.4 g) was purified by column chromatography over silica gel (eluent: CH2Cl2 /CH3OH 98/2). The pure fractions were collected and the solvent was evaporated, yielding 4.7 g of 1,1-dimethylethyl 4-[[(4-amino-5-chloro-2,3-dihydro-7-benzofuranyl)carbonyl]oxy]-1-piperidinecarboxylate (59%) (intermediate 8).

Workup

  1. washThe mixture was washed with water
  2. customThe organic layer was separated
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. customthe solvent was evaporated
  6. customThe residue (7.4 g) was purified by column chromatography over silica gel (eluent: CH2Cl2 /CH3OH 98/2)
  7. customThe pure fractions were collected
  8. customthe solvent was evaporated

Sources & evidence

ORD record
ord-93e9d805ef41497bb90b16380ca33c64
Source dataset
uspto-grants-1999_02
Patent number
US05872131

Reaction notes

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