Tetrahydrofuran → methyl (2S)-1-(6-isobutyl-1,3-benzoxazol-2-yl)-2-piperidinecarboxylate

HRID 1276180Notes

Reaction equation

HRID 1276180 reaction equation
[CH2:1](B(O)O)[CH:2]([CH3:4])[CH3:3].C(=O)([O-])[O-].[K+].[K+].Br[C:15]1[CH:33]=[CH:32][C:18]2[N:19]=[C:20]([N:22]3[CH2:27][CH2:26][CH2:25][CH2:24][C@H:23]3[C:28]([O:30][CH3:31])=[O:29])[O:21][C:17]=2[CH:16]=1.O1CCCC1>C1(C)C=CC=CC=1>[CH2:1]([C:15]1[CH:33]=[CH:32][C:18]2[N:19]=[C:20]([N:22]3[CH2:27][CH2:26][CH2:25][CH2:24][C@H:23]3[C:28]([O:30][CH3:31])=[O:29])[O:21][C:17]=2[CH:16]=1)[CH:2]([CH3:4])[CH3:3]

Participants

6

Reactant 4

HCID 8028TetrahydrofuranHCID 11430Potassium CarbonateHCID 2734395(2-Methylpropyl)boronic acidHCID 9949771methyl (2S)-1-(6-bromo-1,3-benzoxazol-2-yl)-2-piperidinecarboxylate

Product 1

HCID 9839924methyl (2S)-1-(6-isobutyl-1,3-benzoxazol-2-yl)-2-piperidinecarboxylateYield 13.6%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
80 °C

Procedure

Isobutyl boronic acid (475 mg), potassium carbonate (644 mg) and tetrakis triphenylphosphine palladium (269 mg) were added sequentially to a solution of methyl (2S)-1-(6-bromo-1,3-benzoxazol-2-yl)-2-piperidinecarboxylate (790 mg) [see Preparation 40] in toluene:tetrahydrofuran, 60:40 by volume, (20 ml) under nitrogen. The reaction mixture was then heated to 80° C. for 20 hours, after which time the solvent was removed under reduced pressure and the residue partitioned between water and dichloromethane. The organic layer was separated and washed with water, dried over magnesium sulphate and the solvent removed under reduced pressure. The crude product was purified by column chromatography on silica gel eluting with a solvent system of 80:20, by volume, hexane:ethyl acetate to afford methyl (2S)-1-(6-isobutyl-1,3-benzoxazol-2-yl)-2-piperidinecarboxylate (100 mg) as an oil.

Workup

  1. customafter which time the solvent was removed under reduced pressure
  2. customthe residue partitioned between water and dichloromethane
  3. customThe organic layer was separated
  4. washwashed with water
  5. dry with materialdried over magnesium sulphate
  6. customthe solvent removed under reduced pressure
  7. customThe crude product was purified by column chromatography on silica gel eluting with a solvent system of 80:20, by volume, hexane

Sources & evidence

ORD record
ord-4bf44656a5d4416d922ff74b4df1e881
Source dataset
uspto-grants-2000_12
Patent number
US06166011

Reaction notes

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