Dichloromethane → HCID 73603605, compound

HRID 1774591Notes

Reaction equation

HRID 1774591 reaction equation
Br[C:2]1[C:6]([C:7]2[CH:8]=[CH:9][C:10]3[O:15][CH2:14][CH2:13][CH2:12][C:11]=3[CH:16]=2)=[C:5]([CH:17]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])[C:18]([O:20]C)=[O:19])[N:4]([CH3:27])[N:3]=1.C(=O)([O-])[O-].[Na+].[Na+].[CH:34]12[CH2:40][CH:37]([CH2:38][CH2:39]1)[CH:36]=[C:35]2B(O)O.ClCCl>C(COC)OC.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.C(O)C>[CH:34]12[CH2:40][CH:37]([CH2:38][CH2:39]1)[CH:36]=[C:35]2[C:2]1[C:6]([C:7]2[CH:8]=[CH:9][C:10]3[O:15][CH2:14][CH2:13][CH2:12][C:11]=3[CH:16]=2)=[C:5]([CH:17]([O:22][C:23]([CH3:24])([CH3:26])[CH3:25])[C:18]([OH:20])=[O:19])[N:4]([CH3:27])[N:3]=1

Participants

9

Reactant 4

HCID 6344DichloromethaneHCID 10340Sodium CarbonateHCID 44119810Bicyclo[2.2.1]hept-2-en-2-ylboronic acidHCID 90095885HCID 90095885, compound

Product 1

HCID 73603605HCID 73603605, compoundYield 60.5%

Reagents, catalysts & solvents 4

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 702EthanolSolventHCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
140 °C

Procedure

A solution of methyl 2-[3-bromo-4-(3,4-dihydro-2H-1-benzopyran-6-yl)-1-methyl-1H-pyrazol-5-yl]-2-(tert-butoxy)acetate (11i) (50 mg, 0.114 mmol), disodium carbonate (36 mg, 0.343 mmol), and bicyclo[2.2.1]hept-2-en-2-ylboronic acid (19 mg, 0.137 mmol) in a mixture of dimethoxyethane (0.45 mL), ethanol (0.19 mL) and water (0.13 mL) was bubbled with nitrogen for 5 minutes. [1,1′-Bis(diphenylphosphino) ferrocene]dichloropalladium(II), complex with dichloromethane (4.7 mg, 0.006 mmol) was added and the reaction mixture was heated at 140° C. for 2 hours. The solution was concentrated in vacuo. Water (2 mL) was added to the residue and the aqueous layer was washed with diethyl ether (2 mL), acidified with 1M hydrochloric acid until pH 3 and extracted with diethyl ether (2×3 mL). The organic layer was dried over sodium sulfate and concentrated in vacuo. The residue was purified by preparative TLC (dichloromethane/ethyl acetate 45/55+0.5% formic acid) to provide 2-(3-{bicyclo[2.2.1]hept-2-en-2-yl}-4-(3,4-dihydro-2H-1-benzopyran-6-yl)-1-methyl-1H-pyrazol-5-yl)-2-(tert-butoxy)acetic acid (example 15) (30 mg, 0.069 mmol, 60%) as a mixture of diastereoisomers.

Workup

  1. customwas bubbled with nitrogen for 5 minutes
  2. concentrationThe solution was concentrated in vacuo
  3. additionWater (2 mL) was added to the residue
  4. washthe aqueous layer was washed with diethyl ether (2 mL)
  5. extractionextracted with diethyl ether (2×3 mL)
  6. dry with materialThe organic layer was dried over sodium sulfate
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by preparative TLC (dichloromethane/ethyl acetate 45/55+0.5% formic acid)

Sources & evidence

ORD record
ord-28e5406e0f594634aa215edc51a3b698
Source dataset
uspto-grants-2016_02
Patent number
US09260395B2

Reaction notes

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