1,2-Dimethoxyethane → HCID 67339165, compound

HRID 1670121Notes

Reaction equation

HRID 1670121 reaction equation
[CH2:1]([O:3][C:4](=[O:41])[CH2:5][CH2:6][CH2:7][O:8][C:9]1[CH:14]=[CH:13][CH:12]=[C:11]([CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][O:21][C:22]2[CH:27]=[C:26]([C:28](=[O:32])[N:29]([CH3:31])[CH3:30])[CH:25]=[C:24](Br)[CH:23]=2)[C:10]=1[CH2:34][CH2:35][C:36]([O:38][CH2:39][CH3:40])=[O:37])[CH3:2].[F:42][C:43]1[CH:44]=[C:45](B(O)O)[CH:46]=[CH:47][C:48]=1[F:49].C(=O)([O-])[O-].[Cs+].[Cs+].C(COC)OC>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]>[CH2:1]([O:3][C:4](=[O:41])[CH2:5][CH2:6][CH2:7][O:8][C:9]1[CH:14]=[CH:13][CH:12]=[C:11]([CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][O:21][C:22]2[CH:23]=[C:24]([C:46]3[CH:45]=[CH:44][C:43]([F:42])=[C:48]([F:49])[CH:47]=3)[CH:25]=[C:26]([C:28](=[O:32])[N:29]([CH3:31])[CH3:30])[CH:27]=2)[C:10]=1[CH2:34][CH2:35][C:36]([O:38][CH2:39][CH3:40])=[O:37])[CH3:2]

Participants

7

Reactant 4

HCID 80711,2-DimethoxyethaneHCID 10796Cesium carbonateHCID 27343373,4-Difluorobenzeneboronic acidHCID 67338116HCID 67338116, compound

Product 1

HCID 67339165HCID 67339165, compoundYield 97%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolvent

Conditions

Temperature
97 °C

Procedure

To a mixture of 4-{3-[6-(3-bromo-5-dimethylcarbamoyl-phenoxy)-hexyl]-2-(2-ethoxycarbonyl-ethyl)-phenoxy}-butyric acid ethyl ester (150 mg, 0.236 mmol), 3,4-difluorophenylboronic acid (75 mg, 0.472 mmol), PdCl2(dppf) (29 mg, 0.04 mmol) and cesium carbonate (153 mg, 0.472 mmol) was added dimethoxyethane (5 mL) at room temperature under nitrogen atmosphere. The resulting light brown suspension was heated to 97° C. and stirred for 15 h. Then, the reaction mixture was cooled to room temperature and diluted with water (50 mL). The organic compound was extracted into ethyl acetate (2×50 mL) and the combined organic extracts were washed with brine solution (50 mL). The organic layer was dried over anhydrous magnesium sulfate, filtration of the drying agent and removal of the solvent under vacuum gave the crude dark brown residue which was purified by using an ISCO™ (40 g) column chromatography eluting with 30-60% ethyl acetate in hexanes to afford 4-{3-[6-(5-dimethylcarbamoyl-3′,4′-difluoro-biphenyl-3-yloxy)-hexyl]-2-(2-ethoxycarbonyl-ethyl)-phenoxy}-butyric acid ethyl ester (152 mg, 97%) as a colorless oil

Workup

  1. temperatureThen, the reaction mixture was cooled to room temperature
  2. extractionThe organic compound was extracted into ethyl acetate (2×50 mL)
  3. washthe combined organic extracts were washed with brine solution (50 mL)
  4. dry with materialThe organic layer was dried over anhydrous magnesium sulfate, filtration of the drying agent and removal of the solvent under vacuum
  5. customgave the crude dark brown residue which
  6. customwas purified
  7. washeluting with 30-60% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-23109c7306f94eb7a5fd9b56df88362d
Source dataset
uspto-grants-2011_08
Patent number
US07989454B2

Reaction notes

Loading…