Ammonium Chloride → tert-Butyl 3-(3-benzyloxypropyl)-6-[3-(2,2-dimethylpropyl)cyclobutyl]-4-oxo-5-hexynoate

HRID 1912074Notes

Reaction equation

HRID 1912074 reaction equation
Br[C:2](Br)=[CH:3][CH:4]1[CH2:7][CH:6]([CH2:8][C:9]([CH3:12])([CH3:11])[CH3:10])[CH2:5]1.C([Li])CCC.[CH2:19]([O:26][CH2:27][CH2:28][CH2:29][CH:30]([C:39](=[O:44])NCOC)[CH2:31][C:32]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33])[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1.[Cl-].[NH4+]>O1CCCC1>[CH2:19]([O:26][CH2:27][CH2:28][CH2:29][CH:30]([C:39](=[O:44])[C:2]#[C:3][CH:4]1[CH2:7][CH:6]([CH2:8][C:9]([CH3:12])([CH3:11])[CH3:10])[CH2:5]1)[CH2:31][C:32]([O:34][C:35]([CH3:36])([CH3:38])[CH3:37])=[O:33])[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1

Participants

6

Reactant 4

HCID 25517Ammonium ChlorideHCID 71114707tert-Butyl 6-benzyloxy-3-(methoxymethylcarbamoyl)hexanoateHCID 86675042HCID 86675042, compoundHCID 178418339Butyllithium

Product 1

HCID 71127328tert-Butyl 3-(3-benzyloxypropyl)-6-[3-(2,2-dimethylpropyl)cyclobutyl]-4-oxo-5-hexynoateYield 67.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

1-(2,2-dibromovinyl)-3-(2,2-dimethylpropyl)cyclobutane (5 g) and tetrahydrofuran (50 mL) were mixed. To the mixture was added n-butyllithium (1.65 M in hexane) (20.5 mL) dropwise at −78° C. The mixture was stirred at ice temperature for 30 min. and a solution of tert-butyl 6-benzyloxy-3-(methoxymethylcarbamoyl)hexanoate (4.13 g) in tetrahydrofuran (25 mL) was added dropwise to the mixture. After stirring at ice temperature for 20 min., saturated aqueous ammonium chloride was added to the reaction mixture. The mixture was extracted with ethyl acetate. The organic layer was washed with brine, then dried over magnesium sulfate. The magnesium sulfate was filtered off and the filtrate was concentrated in vacuo. The resultant residue was purified by silica gel column chromatography (Eluent: ethyl acetate/hexane=1/20) to give the title compound (3.45 g).

Workup

  1. stirringAfter stirring at ice temperature for 20 min.
  2. extractionThe mixture was extracted with ethyl acetate
  3. washThe organic layer was washed with brine
  4. dry with materialdried over magnesium sulfate
  5. filtrationThe magnesium sulfate was filtered off
  6. concentrationthe filtrate was concentrated in vacuo
  7. customThe resultant residue was purified by silica gel column chromatography (Eluent: ethyl acetate/hexane=1/20)

Sources & evidence

ORD record
ord-8e1c1b07880a44fe903b7f1f9a09e891
Source dataset
uspto-grants-2013_12
Patent number
US08604069B2

Reaction notes

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