Dichloromethane → HCID 23571181, compound

HRID 1823969Notes

Reaction equation

HRID 1823969 reaction equation
Br[C:2]1[S:6][C:5]([C:7]2[CH:8]=[CH:9][C:10]3[CH2:17][CH:16]4[C:18]5([CH2:22][N:21]([CH2:23][C:24]([F:27])([F:26])[F:25])[S:20](=[O:29])(=[O:28])[NH:19]5)[CH:13]([CH2:14][CH2:15]4)[CH2:12][C:11]=3[CH:30]=2)=[N:4][CH:3]=1.[F:31][C:32]1[CH:33]=[C:34](B(O)O)[CH:35]=[CH:36][CH:37]=1.C(=O)([O-])[O-].[K+].[K+].ClCCl>C1(C)C=CC=CC=1.C(O)C.O.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]>[F:31][C:32]1[CH:37]=[C:36]([C:2]2[S:6][C:5]([C:7]3[CH:8]=[CH:9][C:10]4[CH2:17][CH:16]5[C:18]6([CH2:22][N:21]([CH2:23][C:24]([F:27])([F:26])[F:25])[S:20](=[O:29])(=[O:28])[NH:19]6)[CH:13]([CH2:14][CH2:15]5)[CH2:12][C:11]=4[CH:30]=3)=[N:4][CH:3]=2)[CH:35]=[CH:34][CH:33]=1

Participants

9

Reactant 4

HCID 6344DichloromethaneHCID 11430Potassium CarbonateHCID 27339863-Fluorophenylboronic acidHCID 22147984HCID 22147984, compound

Product 1

HCID 23571181HCID 23571181, compoundYield 27%

Reagents, catalysts & solvents 4

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 702EthanolSolventHCID 962WaterSolventHCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of the bromide from Step 2 (20 mg) in toluene (0.5 mL), ethanol (0.25 mL) and water (0.25 mL) were added 3-fluorophenylboronic acid (8 mg), potassium carbonate (26 mg) and [1,1′bis(diphenylphosphino)ferrocene]dichloropalladium(II), complex with dichloromethane (3 mg). The mixture was heated in a microwave at 100° C. for 5 min. Additional catalyst was added and the mixture was heated at 100° C. for a further 10 min. The reaction mixture was poured into satd. NaHCO3(aq) and extracted with ethyl acetate (×2). The combined organic extracts were washed with brine, dried over Na2SO4 and concentrated. Chromatography on silica eluting with 25% ethyl acetate in hexane gave the title compound (5.5 mg, 27%). δ (1H, 400 MHz, CDCl3) 1.31–1.41 (2H, m), 1.71–1.77 (2H, m), 2.47–2.51 (2H, m), 2.72–2.84 (2H, m), 3.25–3.29 (2H, m), 3.45 (2H, s), 3.70 (2H, q, J=8.7 Hz), 4.93 (1H, s), 7.01–7.06 (1H, m), 7.18 (1H, d, J=7.8 Hz), 7.28–7.31 (1H, m), 7.37–7.41 (2H, m), 7.68 (1H, dd, J=7.8, 1.6 Hz), 7.73 (1H, d, J=1.2 Hz), 8.00 (1H, s); MS (ES+) 538 ([MH]+).

Workup

  1. additionAdditional catalyst was added
  2. temperaturethe mixture was heated at 100° C. for a further 10 min
  3. additionThe reaction mixture was poured into satd
  4. extractionNaHCO3(aq) and extracted with ethyl acetate (×2)
  5. washThe combined organic extracts were washed with brine
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-be752617972a4580b17e26b31c9b6da2
Source dataset
uspto-grants-2006_05
Patent number
US07041689B2

Reaction notes

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