Acetate → HCID 67811854, compound

HRID 2401368Notes

Reaction equation

HRID 2401368 reaction equation
C([O:4][CH2:5][C:6]1[O:10][N:9]=[C:8]([CH3:11])[C:7]=1B1OC(C)(C)C(C)(C)O1)(=O)C.Br[C:22]1[S:23][C:24]([CH3:37])=[C:25]([CH3:36])[C:26]=1[C:27]([C:29]1[CH:34]=[CH:33][C:32]([Cl:35])=[CH:31][CH:30]=1)=[O:28].C([O-])([O-])=O.[K+].[K+].N#N.[OH-].[Na+].C([O-])(=O)C.Cl.C>O1CCOCC1.O.CC(OC)(C)C.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].C(Cl)Cl>[Cl:35][C:32]1[CH:31]=[CH:30][C:29]([C:27]([C:26]2[C:25]([CH3:36])=[C:24]([CH3:37])[S:23][C:22]=2[C:7]2[C:8]([CH3:11])=[N:9][O:10][C:6]=2[CH2:5][OH:4])=[O:28])=[CH:34][CH:33]=1

Participants

13

Reactant 8

HCID 175AcetateHCID 297MethaneHCID 313Hydrochloric AcidHCID 947NitrogenHCID 11430Potassium CarbonateHCID 14798Sodium HydroxideHCID 67813348HCID 67813348, compoundHCID 678177175-Isoxazolemethanol, 3-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-, 5-acetate

Product 1

HCID 67811854HCID 67811854, compoundYield 79.1%

Reagents, catalysts & solvents 4

HCID 178418807HCID 178418807, compoundCatalystHCID 962WaterSolventHCID 15413tert-Butyl methyl etherSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
45 °C

Procedure

To a solution of (3-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)isoxazol-5-yl)methyl acetate (0.865 g, 3.08 mmol) and (2-bromo-4,5-dimethylthiophen-3-yl)(4-chlorophenyl)methanone (0.534 g, 1.619 mmol) in 1,4-dioxane (7 mL) and water (2 mL) was added PdCl2(dppf)-CH2Cl2 adduct (0.090 g, 0.110 mmol) and K2CO3 (0.560 g, 4.05 mmol). The bi-phasic mixture was heated to 95° C. under a constant stream of N2 (g). After 5 h, the mixture was cooled to 45° C. and aqueous 1 N NaOH (4.0 mL, 4.00 mmol) was introduced. After an additional 1 h, LC-MS analysis shows complete conversion of acetate to alcohol. The mixture was cooled to room temperature, 1 N HCl was added to acidify the aqueous layer (pH ˜1) and the aqueous layer extracted MTBE (2×). The combined organic layer was washed with saturated NaHCO3, brine, dried over Na2SO4, and concentrated to give a dark brown oil. The oil was diluted with MTBE and stirred over activated charcoal for 15 min, then filtered over a plug of silica and Celite. The filter cake was washed with MTBE (2×) and subsequently concentration gave a brown oil. The resultant oil was purified on Biotage system (gradient elution 5% EtOAc:95% Hexanes to 40% EtOAc:60% Hexanes) to give the titled compound as a yellow oil (0.463 g, 1.28 mmol, 79% yield). LC/MS m/z 362 [M+H]+.

Workup

  1. waitAfter an additional 1 h
  2. temperatureThe mixture was cooled to room temperature
  3. extractionthe aqueous layer extracted MTBE (2×)
  4. washThe combined organic layer was washed with saturated NaHCO3, brine
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated
  7. customto give a dark brown oil
  8. filtrationfiltered over a plug of silica and Celite
  9. washThe filter cake was washed with MTBE (2×) and subsequently concentration
  10. customgave a brown oil
  11. customThe resultant oil was purified on Biotage system (gradient elution 5% EtOAc:95% Hexanes to 40% EtOAc:60% Hexanes)

Sources & evidence

ORD record
ord-379418dde3254231a98eb63eb3ab36b8
Source dataset
uspto-grants-2014_08
Patent number
US08796261B2

Reaction notes

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