tert-Butyl 4-oxopiperidine-1-carboxylate → 4-Hydroxy-4-(3-(1-hydroxyethyl)benzo[b]thiophen-2-yl)-1-(t-butyloxycarbonyl)piperidine

HRID 1837481Notes

Reaction equation

HRID 1837481 reaction equation
[OH:1][CH:2]([C:4]1[C:5]2[CH:12]=[CH:11][CH:10]=[CH:9][C:6]=2[S:7][CH:8]=1)[CH3:3].C([Li])CCC.[C:18]([O:22][C:23]([N:25]1[CH2:30][CH2:29][C:28](=[O:31])[CH2:27][CH2:26]1)=[O:24])([CH3:21])([CH3:20])[CH3:19]>O1CCCC1.[Cl-].[Na+].O>[OH:31][C:28]1([C:8]2[S:7][C:6]3[CH:9]=[CH:10][CH:11]=[CH:12][C:5]=3[C:4]=2[CH:2]([OH:1])[CH3:3])[CH2:27][CH2:26][N:25]([C:23]([O:22][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:24])[CH2:30][CH2:29]1

Participants

6

Reactant 3

HCID 735900tert-Butyl 4-oxopiperidine-1-carboxylateHCID 129927691-(1-Benzothiophen-3-yl)ethan-1-olHCID 178418339Butyllithium

Product 1

HCID 129927704-Hydroxy-4-(3-(1-hydroxyethyl)benzo[b]thiophen-2-yl)-1-(t-butyloxycarbonyl)piperidineYield 87.1%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
0 °C

Procedure

Scheme IA, Step A: To a solution of 3-(1-hydroxyethyl)benzo[b]thiophene (2.036 g, 11.4 mmol) in tetrahydrofuran (75 mL) at −78° C. was added a solution of n-butyllithium (15.7 mL, 25.1 mmol, 1.6 M in hexanes). The solution was warmed to 0° C. for one hour then recooled to −78° C. A solution of 1-t-butyloxycarbonyl-4-piperidone (2.503 g, 12.6 mmol) in tetrahydrofuran was added dropwise and the mixture was warmed to 20° C. After stirring for 6 hours at 20° C. the mixture was diluted with brine and extracted 3 times with ethyl acetate. The combined organics were dried over sodium sulfate then filtered and evaporated. The residue was purified using silica gel chromatography (dichloromethane/5% methanol in dichloromethane gradient eluent) to give 3.75 g (87%) of the intermediate title compound as a yellow amorphous solid. FDMS m/e=378 (M++1).

Workup

  1. customthen recooled to −78° C
  2. temperaturethe mixture was warmed to 20° C
  3. extractionextracted 3 times with ethyl acetate
  4. dry with materialThe combined organics were dried over sodium sulfate
  5. filtrationthen filtered
  6. customevaporated
  7. customThe residue was purified

Sources & evidence

ORD record
ord-3328115f9fba4e78bfa5d05455d0e2f2
Source dataset
uspto-grants-2004_08
Patent number
US06784180B2

Reaction notes

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