Dichloromethane → Ethyl 4-methyl-5-(spiro[4.5]dec-7-en-8-yl)isoxazole-3-carboxylate

HRID 1478152Notes

Reaction equation

HRID 1478152 reaction equation
CC1(C)C(C)(C)OB([C:9]2[CH2:18][CH2:17][C:12]3([CH2:16][CH2:15][CH2:14][CH2:13]3)[CH2:11][CH:10]=2)O1.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>CC#N.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>[CH3:31][C:22]1[C:23]([C:26]([O:28][CH2:29][CH3:30])=[O:27])=[N:24][O:25][C:21]=1[C:9]1[CH2:18][CH2:17][C:12]2([CH2:13][CH2:14][CH2:15][CH2:16]2)[CH2:11][CH:10]=1

Participants

8

Reactant 4

HCID 6344DichloromethaneHCID 11430Potassium CarbonateHCID 231415764,4,5,5-Tetramethyl-2-(spiro[4.5]dec-7-EN-8-YL)-1,3,2-dioxaborolaneHCID 58828802Ethyl 5-bromo-4-methyl-1,2-oxazole-3-carboxylate2×

Product 1

HCID 118511037Ethyl 4-methyl-5-(spiro[4.5]dec-7-en-8-yl)isoxazole-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 4,4,5,5-tetramethyl-2-(spiro[4.5]dec-7-en-8-yl)-1,3,2-dioxaborolane (168 mg, 0.641 mmol) in MeCN (2 mL), ethyl 5-bromo-4-methylisoxazole-3-carboxylate (Intermediate A) (150 mg, 0.641 mmol) was added followed by K2CO3 (266 mg, 1.923 mmol), PdCl2(dppf).CH2Cl2 adduct (Alfa Aesar) (52.3 mg, 0.064 mmol) and water (1 mL). The vial was flushed with nitrogen, sealed and treated in the microwave (Biotage Smith Initiator) at 90° C. for 1 hour. The reaction mixture was partitioned between water (20 mL) and EtOAc (20 mL) and the organic phase was washed with brine (20 mL), dried over MgSO4, filtered and concentrated under reduced pressure to give an orange oil. The crude material was adsorbed onto silica and purification by chromatography eluting with 0-30% EtOAc in iso-hexane afforded the title compound;

Workup

  1. additionwas added
  2. customThe vial was flushed with nitrogen
  3. customsealed
  4. additiontreated in the microwave (Biotage Smith Initiator) at 90° C. for 1 hour
  5. customThe reaction mixture was partitioned between water (20 mL) and EtOAc (20 mL)
  6. washthe organic phase was washed with brine (20 mL)
  7. dry with materialdried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. customto give an orange oil
  11. customThe crude material was adsorbed onto silica and purification by chromatography
  12. washeluting with 0-30% EtOAc in iso-hexane

Sources & evidence

ORD record
ord-46be4304ecb1432689237f5edfee5083
Source dataset
uspto-grants-2016_08
Patent number
US09403810B2

Reaction notes

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