Water → [2-Chloro-4-(2,4-difluoro-phenylamino)-phenyl]-(3'-hydroxymethyl-4-methyl-biphenyl-3-yl)-methanone

HRID 1012635Notes

Reaction equation

HRID 1012635 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([NH:8][C:9]2[CH:14]=[CH:13][C:12]([F:15])=[CH:11][C:10]=2[F:16])[CH:5]=[CH:4][C:3]=1[C:17]([C:19]1[CH:24]=[C:23](I)[CH:22]=[CH:21][C:20]=1[CH3:26])=[O:18].[OH:27][CH2:28][C:29]1[CH:30]=[C:31](B(O)O)[CH:32]=[CH:33][CH:34]=1.C([O-])(O)=O.[Na+].O>COCCOC.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.CCOC(C)=O>[Cl:1][C:2]1[CH:7]=[C:6]([NH:8][C:9]2[CH:14]=[CH:13][C:12]([F:15])=[CH:11][C:10]=2[F:16])[CH:5]=[CH:4][C:3]=1[C:17]([C:19]1[CH:24]=[C:23]([C:33]2[CH:32]=[CH:31][CH:30]=[C:29]([CH2:28][OH:27])[CH:34]=2)[CH:22]=[CH:21][C:20]=1[CH3:26])=[O:18]

Participants

8

Reactant 4

HCID 962WaterHCID 516892Sodium BicarbonateHCID 2734662[3-(Hydroxymethyl)phenyl]boronic acidHCID 67314444[2-Chloro-4-(2,4-difluoro-phenylamino)-phenyl]-(5-iodo-2-methyl-phenyl)-methanone

Product 1

HCID 58677560[2-Chloro-4-(2,4-difluoro-phenylamino)-phenyl]-(3'-hydroxymethyl-4-methyl-biphenyl-3-yl)-methanone

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 80711,2-DimethoxyethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

Compound 495 (0.039 g, 0.081 mmol) was dissolved in 1,2-dimethoxyethane (0.8 mL) in a screw cap vessel. 3-(Hydroxymethyl)phenylboronic acid (0.015 g, 0.097 mmol) and saturated aqueous NaHCO3 (0.4 mL) were added. Argon was blown over the mixture and Pd(PPh3)4 (0.005 g, 0.004 mmol) was added. The reaction mixture was stirred at reflux temperature under an argon atmosphere for 2 h. H2O and EtOAc were added and the water phase was extracted with EtOAc (×2). The combined organic phases were dried (MgSO4), filtered and concentrated in vacuo. The crude product was purified by flash chromatography using EtOAc/petroleum ether (40-60) 1:1 as the eluent. This afforded the title compound as oil. 13C NMR (CDCl3) δ 196.3, 159.1 (dd), 155.5 (dd), 147.8, 141.5, 140.6, 139.6, 138.3, 137.0, 135.3, 133.7, 131.8, 129.4, 129.1, 128.0, 126.3, 126.0, 125.6, 124.4 (dd), 124.3 (dd), 116.3, 112.8, 111.6 (dd), 104.9 (dd), 65.3, 20.1

Workup

  1. customcap vessel
  2. additionwas added
  3. temperatureat reflux temperature under an argon atmosphere for 2 h
  4. extractionthe water phase was extracted with EtOAc (×2)
  5. dry with materialThe combined organic phases were dried (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe crude product was purified by flash chromatography

Sources & evidence

ORD record
ord-bbbc955c9d024ddfa0cd31e5a24e03fb
Source dataset
uspto-grants-2011_07
Patent number
US07977387B2

Reaction notes

Loading…