Dimethylformamide → tert-Butyl 6-benzyloxy-3-[4-cyclopropyl-5-[3-(2,2-dimethylpropyl)cyclobutyl]isoxazol-3-yl]hexanoate

HRID 1912077Notes

Reaction equation

HRID 1912077 reaction equation
[CH2:1]([O:8][CH2:9][CH2:10][CH2:11][CH:12]([C:21]1[C:25](I)=[C:24]([CH:27]2[CH2:30][CH:29]([CH2:31][C:32]([CH3:35])([CH3:34])[CH3:33])[CH2:28]2)[O:23][N:22]=1)[CH2:13][C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH:36]1(B2OC(C)(C)C(C)(C)O2)[CH2:38][CH2:37]1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].CN(C=O)C>O>[CH2:1]([O:8][CH2:9][CH2:10][CH2:11][CH:12]([C:21]1[C:25]([CH:36]2[CH2:38][CH2:37]2)=[C:24]([CH:27]2[CH2:30][CH:29]([CH2:31][C:32]([CH3:35])([CH3:34])[CH3:33])[CH2:28]2)[O:23][N:22]=1)[CH2:13][C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 62657Potassium Phosphate, TribasicHCID 27580152-Cyclopropyl-4,4,5,5-tetramethyl-1,3,2-dioxaborolaneHCID 71127330tert-Butyl 6-benzyloxy-3-{5-[3-(2,2-dimethylpropyl)cyclobutyl]-4-iodoisoxazole-3-yl}hexanoate

Product 1

HCID 71127331tert-Butyl 6-benzyloxy-3-[4-cyclopropyl-5-[3-(2,2-dimethylpropyl)cyclobutyl]isoxazol-3-yl]hexanoateYield 27.3%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
80 °C

Procedure

tert-Butyl 6-benzyloxy-3-{5-[3-(2,2-dimethylpropyl)cyclobutyl]-4-iodoisoxazole-3-yl}hexanoate (4.20 g), 2-cyclopropyl-4,4,5,5-tetramethyl-[1,3,2]dioxaborolane (2.34 g), tripotassium phosphate (5.92 g), DMF (90 mL) and water (10 mL) were mixed. The mixture was degassed by bubbling argon gas. To the mixture was added PdCl2(PPh3)2 (734 mg). The mixture was stirred at 80° C. for 1 hr. To the reaction mixture was added ethyl acetate, and then the mixture was filtered. The aqueous layer was removed, and the organic layer was washed with water and 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=1/25) to give the title compound (980 mg). A mixture of the title compound and impurities thereof (1.24 g) was also obtained.

Workup

  1. customThe mixture was degassed
  2. customby bubbling argon gas
  3. additionTo the mixture was added PdCl2(PPh3)2 (734 mg)
  4. additionTo the reaction mixture was added ethyl acetate
  5. filtrationthe mixture was filtered
  6. customThe aqueous layer was removed
  7. washthe organic layer was washed with water and brine
  8. dry with materialdried over magnesium sulfate
  9. filtrationThe magnesium sulfate was filtered off
  10. concentrationthe filtrate was concentrated in vacuo
  11. customThe resultant residue was purified by silica gel column chromatography (Eluent: ethyl acetate/hexane=1/25)

Sources & evidence

ORD record
ord-09620ebcc6164479a0d7bf5b6167a5e7
Source dataset
uspto-grants-2013_12
Patent number
US08604069B2

Reaction notes

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