tert-Butyl 4-oxopiperidine-1-carboxylate → Tert-butyl 4-(4-chloro-2-(4,4-dimethyl-4,5-dihydrooxazol-2-yl)phenyl)-4-hydroxypiperidine-1-carboxylate

HRID 917114Notes

Reaction equation

HRID 917114 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([Cl:8])=[CH:4][C:3]=1[C:9]1[O:10][CH2:11][C:12]([CH3:15])([CH3:14])[N:13]=1.C([Li])CCC.[C:21]([O:25][C:26]([N:28]1[CH2:33][CH2:32][C:31](=[O:34])[CH2:30][CH2:29]1)=[O:27])([CH3:24])([CH3:23])[CH3:22]>O1CCCC1>[C:21]([O:25][C:26]([N:28]1[CH2:33][CH2:32][C:31]([C:2]2[CH:7]=[CH:6][C:5]([Cl:8])=[CH:4][C:3]=2[C:9]2[O:10][CH2:11][C:12]([CH3:15])([CH3:14])[N:13]=2)([OH:34])[CH2:30][CH2:29]1)=[O:27])([CH3:24])([CH3:22])[CH3:23]

Participants

5

Reactant 3

HCID 735900tert-Butyl 4-oxopiperidine-1-carboxylateHCID 231369142-(2-Bromo-5-chlorophenyl)-4,4-dimethyl-4,5-dihydrooxazoleHCID 178418339Butyllithium

Product 1

HCID 46835566Tert-butyl 4-(4-chloro-2-(4,4-dimethyl-4,5-dihydrooxazol-2-yl)phenyl)-4-hydroxypiperidine-1-carboxylate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

To a cold (−78° C.) solution of the product of step 1 (1.09 g, 4.63 mmol) in anhydrous tetrahydrofuran (10 mL) was added a solution of n-butyllithium (1.6 M in hexanes, 2.89 mL, 4.63 mmol) and the contents of the reaction were allowed to react for 0.5 h. A solution of 4-oxo-piperidine-1-carboxylic acid tert-butyl ester (922 mg, 4.63 mmol) in tetrahydrofuran (10 mL) was added and the combined contents stirred for 2 h at −78° C. Reaction was quenched by the addition of saturated aqueous ammonium chloride (30 mL), followed by warming to rt. The biphasic mixture was extracted with ethyl acetate (150 mL); washed with water and brine; dried over magnesium sulfate; filtered and concentrated. 4-[4-Chloro-2-(4,4-dimethyl-4,5-dihydro-oxazol-2-yl)-phenyl]-4-hydroxy-piperidine-1-carboxylic acid tert-butyl ester was isolated (412 mg, 22%) following silica gel chromatography (80% hexanes/20% ethyl acetate).

Workup

  1. customto react for 0.5 h
  2. customReaction
  3. customwas quenched by the addition of saturated aqueous ammonium chloride (30 mL)
  4. temperatureby warming to rt
  5. extractionThe biphasic mixture was extracted with ethyl acetate (150 mL)
  6. washwashed with water and brine
  7. dry with materialdried over magnesium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-066b7d85fd61498c917d9ac15c4671bc
Source dataset
uspto-grants-2007_09
Patent number
US07271176B2

Reaction notes

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