tert-Butyl 2-methyl-4-oxopiperidine-1-carboxylate → HCID 22495736, compound

HRID 1815875Notes

Reaction equation

HRID 1815875 reaction equation
[F:1][C:2]1[C:3]([F:12])=[C:4](Br)[C:5]2[O:9][CH:8]=[CH:7][C:6]=2[CH:10]=1.C([Li])(C)(C)C.[C:18]([O:22][C:23]([N:25]1[CH2:30][CH2:29][C:28](=[O:31])[CH2:27][CH:26]1[CH3:32])=[O:24])([CH3:21])([CH3:20])[CH3:19]>O1CCCC1>[C:18]([O:22][C:23]([N:25]1[CH2:30][CH2:29][C:28]([OH:31])([C:4]2[C:5]3[O:9][CH:8]=[CH:7][C:6]=3[CH:10]=[C:2]([F:1])[C:3]=2[F:12])[CH2:27][CH:26]1[CH3:32])=[O:24])([CH3:21])([CH3:19])[CH3:20]

Participants

5

Reactant 3

HCID 12992764tert-Butyl 2-methyl-4-oxopiperidine-1-carboxylateHCID 22277250HCID 22277250, compoundHCID 178418306HCID 178418306, compound

Product 1

HCID 22495736HCID 22495736, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of 2.28 gm (9.8 mMol) 5,6-difluoro-7-bromobenzofuran in 30 mL tetrahydrofuran was cooled to −78° C. and then 9.8 mL (19.6 mMol) tert-butyllithium (1.7M in tetrahydrofuran) were added. After stirring for 30 minutes, a solution of 1.9 gm (8.9 mMol) 1-(tert-butoxycarbonyl)-2-methyl-4-oxo-piperidine in 20 mL tetrahydrofuran was added dropwise over 30 minutes. The reaction mixture was allowed to warm to room temperature over 16 hours and was then concentrated under reduced pressure. The residue was dissolved in 200 mL ethyl acetate and extracted sequentially with 50 mL 1N hydrochloric acid, saturated aqueous sodium bicarbonate, and saturated aqueous sodium chloride. The remaining organic phase was dried over magnesium sulfate and concentrated under reduced pressure to provide 1-(tert-butoxycarbonyl)-2-methyl-4-hydroxy-4-(5,6-difluorobenzofur-7-yl)piperidine. This alcohol was converted to a mixture of the title compounds essentially as described in EXAMPLE 1.

Workup

  1. concentrationwas then concentrated under reduced pressure
  2. dissolutionThe residue was dissolved in 200 mL ethyl acetate
  3. extractionextracted sequentially with 50 mL 1N hydrochloric acid, saturated aqueous sodium bicarbonate, and saturated aqueous sodium chloride
  4. dry with materialThe remaining organic phase was dried over magnesium sulfate
  5. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-a0aaf7cd703b4fb6b8f28cdc972bc5e4
Source dataset
uspto-grants-2005_04
Patent number
US06881733B1

Reaction notes

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