Dichloromethane → Ethyl 5-(4-isopropoxycyclohex-1-en-1-yl)-4-methylisoxazole-3-carboxylate

HRID 1478166Notes

Reaction equation

HRID 1478166 reaction equation
[CH:1]([O:4][CH:5]1[CH2:10][CH2:9][C:8](B2OC(C)(C)C(C)(C)O2)=[CH:7][CH2:6]1)([CH3:3])[CH3:2].Br[C:21]1[O:25][N:24]=[C:23]([C:26]([O:28][CH2:29][CH3:30])=[O:27])[C:22]=1[CH3:31].C([O-])([O-])=O.[K+].[K+].C(Cl)Cl>C(#N)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].O>[CH:1]([O:4][CH:5]1[CH2:10][CH2:9][C:8]([C:21]2[O:25][N:24]=[C:23]([C:26]([O:28][CH2:29][CH3:30])=[O:27])[C:22]=2[CH3:31])=[CH:7][CH2:6]1)([CH3:2])[CH3:3]

Participants

8

Reactant 4

HCID 6344DichloromethaneHCID 11430Potassium CarbonateHCID 58828802Ethyl 5-bromo-4-methyl-1,2-oxazole-3-carboxylate2×HCID 1311438834,4,5,5-Tetramethyl-2-[4-(propan-2-yloxy)cyclohex-1-en-1-yl]-1,3,2-dioxaborolane

Product 1

HCID 118511109Ethyl 5-(4-isopropoxycyclohex-1-en-1-yl)-4-methylisoxazole-3-carboxylate

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolventHCID 6342AcetonitrileSolvent

Procedure

To a 2-5 mL microwave vial containing a solution of [2-(4-isopropoxycyclohex-1-en-1-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane] (375 mg, 1.410 mmol) in acetonitrile (2 mL), ethyl 5-bromo-4-methylisoxazole-3-carboxylate (Intermediate A) (330 mg, 1.410 mmol) was added followed by K2CO3 (585 mg, 4.23 mmol), PdCl2(dppf).CH2Cl2 adduct (11.51 mg, 0.014 mmol) and water (2 mL). The vial was flushed with nitrogen and treated in the microwave (Biotage Smith Initiator) at 80° C. for 90 minutes. The reaction mixture was partitioned between water (30 mL) and EtOAc (30 mL). The organic phase was washed with brine (30 mL), dried over MgSO4, filtered through a Celite® pad and the filtrate was concentrated under reduced pressure. The crude material was adsorbed onto silica and purification by chromatography eluting with 0-60% EtOAc in iso-hexane afforded the title compound;

Workup

  1. customThe vial was flushed with nitrogen
  2. additiontreated in the microwave (Biotage Smith Initiator) at 80° C. for 90 minutes
  3. customThe reaction mixture was partitioned between water (30 mL) and EtOAc (30 mL)
  4. washThe organic phase was washed with brine (30 mL)
  5. dry with materialdried over MgSO4
  6. filtrationfiltered through a Celite® pad
  7. concentrationthe filtrate was concentrated under reduced pressure
  8. customThe crude material was adsorbed onto silica and purification by chromatography
  9. washeluting with 0-60% EtOAc in iso-hexane

Sources & evidence

ORD record
ord-9ac98aa7c5e2425f99779c91a6bf8d7a
Source dataset
uspto-grants-2016_08
Patent number
US09403810B2

Reaction notes

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