1-(2-Bromophenyl)-1H-pyrazole → HCID 89726434, compound

HRID 1777742Notes

Reaction equation

HRID 1777742 reaction equation
Br[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[N:8]1[CH:12]=[CH:11][CH:10]=[N:9]1.[Cl-].[C:14]([O:18][C:19](=[O:22])[CH2:20][Zn+])([CH3:17])([CH3:16])[CH3:15]>C1COCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].C1([C-]2C(C3C=CC=CC=3)=C(C3C=CC=CC=3)C(C3C=CC=CC=3)=C2C2C=CC=CC=2)C=CC=CC=1.C(P(C(C)(C)C)[C-]1C=CC=C1)(C)(C)C.[Fe+2]>[C:14]([O:18][C:19](=[O:22])[CH2:20][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[N:8]1[CH:12]=[CH:11][CH:10]=[N:9]1)([CH3:17])([CH3:16])[CH3:15]

Participants

6

Reactant 2

HCID 27954331-(2-Bromophenyl)-1H-pyrazoleHCID 178451183HCID 178451183, compound

Product 1

HCID 89726434HCID 89726434, compound

Reagents, catalysts & solvents 3

HCID 6505921(1E,4E)-1,5-diphenylpenta-1,4-dien-3-one; palladiumCatalystHCID 129828017Ditert-butyl(cyclopenta-2,4-dien-1-yl)phosphane;iron(2+);(2,3,4,5-tetraphenylcyclopenta-1,4-dien-1-yl)benzeneCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
70 °C

Procedure

A mixture of 1-(2-bromophenyl)-1H-pyrazole (230 mg), 2-tert-butoxy-2-oxoethylzinc chloride (0.5M in Et2O, 2.2 mL), Pd(dba)2 (28.8 mg) and 1,2,3,4,5-pentaphenyl-1′-(di-tert-butylphosphino)ferrocene (37.4 mg) in THF (3 mL) was degassed with argon and was stirred at 70° C. overnight. The reaction mixture was diluted with EA and washed with water and brine, dried (Na2SO4), filtered off and evaporated to dryness. The residue was purified by CC (Biotage, SNAP 25 g cartridge, solvent A: Hept; solvent B: EA; gradient in % B: 8 for 4CV, 8 to 66 over 10CV, 66 for 2CV, 66 to 100 over 1CV, 100 for 6CV. Second CC: SNAP 10 g cartridge, solvent A: DCM; solvent B: MeOH; gradient in % B: 0 for 15CV, 0 to 1 over 1CV, 1 for 5CV, 1 to 5 over 1CV, 5 for 2CV, 5 to 10 over 1CV, 10 for 2CV, 10 to 20 over 1CV, 20 for 2CV) to afford 33 mg of (2-pyrazol-1-yl-phenyl)-acetic acid tert-butyl ester. LC-MS (B): tR=0.87 min; [M+H]+: 259.34.

Workup

  1. customwas degassed with argon
  2. additionThe reaction mixture was diluted with EA
  3. washwashed with water and brine
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered off
  6. customevaporated to dryness
  7. customThe residue was purified by CC (Biotage, SNAP 25 g cartridge, solvent A: Hept; solvent B: EA; gradient in % B: 8 for 4CV, 8 to 66 over 10CV, 66 for 2CV, 66 to 100 over 1CV, 100 for 6CV. Second CC: SNAP 10 g cartridge, solvent A: DCM; solvent B: MeOH; gradient in % B: 0 for 15CV, 0 to 1 over 1CV, 1 for 5CV, 1 to 5 over 1CV, 5 for 2CV, 5 to 10 over 1CV, 10 for 2CV, 10 to 20 over 1CV, 20 for 2CV)

Sources & evidence

ORD record
ord-0827fe5cb1f44b1a8c1d7be346445d89
Source dataset
uspto-grants-2016_02
Patent number
US09266876B2

Reaction notes

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