1-Boc-3-hydroxypiperidine → 1-Boc-3-hydroxypiperidine

HRID 1269828Notes

Reaction equation

HRID 1269828 reaction equation
[CH3:1][C:2]1[C:10]([OH:11])=[CH:9][CH:8]=[C:7]2[C:3]=1[CH:4]=[N:5][NH:6]2.[OH:12][CH:13]1[CH2:18][CH2:17][CH2:16][N:15]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:14]1>O1CCCC1>[CH3:1][C:2]1[C:10]([O:11][CH:17]2[CH2:18][CH2:13][CH2:14][N:15]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:16]2)=[CH:9][CH:8]=[C:7]2[C:3]=1[CH:4]=[N:5][NH:6]2.[OH:12][CH:13]1[CH2:18][CH2:17][CH2:16][N:15]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:14]1

Participants

5

Reactant 2

HCID 5456991-Boc-3-hydroxypiperidineHCID 229335464-methyl-1H-indazol-5-ol

Product 2

HCID 5456991-Boc-3-hydroxypiperidineHCID 18447538t-butyl 3-[(4-methyl-1H-indazol-5-yl)oxy]piperidine-1-carboxylate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of dibenzyl dicarboxylate (10.1 g, 33.9 mmol) in tetrahydrofuran (50 ml) was added dropwise to a mixture of the 5-hydroxy-4-methyl-1H-indazole (4.17 g, 28.1 mmol) obtained in Example 402, t-butyl 3-hydroxypiperidine-1-carboxylate (5.62 g, 27.9 mmol) and tetrahydrofuran (100 ml) under ice-cooling. After 30 minutes, the mixture thus obtained was warmed up to room temperature and stirred for 16 hours. The reaction mixture was concentrated and then a 1N-aqueous sodium hydroxide solution (250 ml) was added thereto, followed by extraction with chloroform (150 ml) (three times). The organic layer was washed with a saturated aqueous sodium chloride solution and dried over magnesium sulfate. The solvent was distilled off under reduced pressure and the resulting residue was purified by a silica gel column chromatography (eluent: hexane/ethyl acetate=3/1 to 2/1) to obtain a crude product t-butyl 3-[(4-methyl-1H-indazol-5-yl)oxy]piperidine-1-carboxylate (a mixture with t-butyl 3-hydroxypiperidine-1-carboxylate, 3.46 g).

Workup

  1. temperaturecooling
  2. customthe mixture thus obtained
  3. concentrationThe reaction mixture was concentrated
  4. additiona 1N-aqueous sodium hydroxide solution (250 ml) was added
  5. extractionfollowed by extraction with chloroform (150 ml) (three times)
  6. washThe organic layer was washed with a saturated aqueous sodium chloride solution
  7. dry with materialdried over magnesium sulfate
  8. distillationThe solvent was distilled off under reduced pressure
  9. customthe resulting residue was purified by a silica gel column chromatography (eluent: hexane/ethyl acetate=3/1 to 2/1)

Sources & evidence

ORD record
ord-e0bafcfe847e4948a12bcbb797741ebd
Source dataset
uspto-grants-2007_04
Patent number
US07199147B2

Reaction notes

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