Methanol → Ethyl 3-(4-((5-(4-chlorophenyl)-2,2-dimethyl-2,3-dihydrobenzofuran-7-yl)methoxy)phenyl)-2-methylpropanoate

HRID 1876445Notes

Reaction equation

HRID 1876445 reaction equation
Br[C:2]1[CH:3]=[C:4]([CH2:13][O:14][C:15]2[CH:20]=[CH:19][C:18]([CH2:21][CH:22]([CH3:26])[C:23]([OH:25])=[O:24])=[CH:17][CH:16]=2)[C:5]2[O:9][C:8]([CH3:11])([CH3:10])[CH2:7][C:6]=2[CH:12]=1.[Cl:27][C:28]1[CH:33]=[CH:32][C:31](B(O)O)=[CH:30][CH:29]=1.C(=O)(O)[O-].[Na+].CO.[C:44](OCC)(=O)[CH3:45]>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.O.C1(C)C=CC=CC=1>[Cl:27][C:28]1[CH:33]=[CH:32][C:31]([C:2]2[CH:3]=[C:4]([CH2:13][O:14][C:15]3[CH:20]=[CH:19][C:18]([CH2:21][CH:22]([CH3:26])[C:23]([O:25][CH2:44][CH3:45])=[O:24])=[CH:17][CH:16]=3)[C:5]3[O:9][C:8]([CH3:11])([CH3:10])[CH2:7][C:6]=3[CH:12]=2)=[CH:30][CH:29]=1

Participants

9

Reactant 5

HCID 887MethanolHCID 8857Ethyl AcetateHCID 742994-Chlorophenylboronic acidHCID 516892Sodium BicarbonateHCID 58566408HCID 58566408, compound

Product 1

HCID 67406232Ethyl 3-(4-((5-(4-chlorophenyl)-2,2-dimethyl-2,3-dihydrobenzofuran-7-yl)methoxy)phenyl)-2-methylpropanoate

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 1140TolueneSolvent

Procedure

A solution of ethyl 3-(4-((5-bromo-2,2-dimethyl-2,3-dihydrobenzofuran-7-yl)methoxy)phenyl)-2-methylpropanoate (110) (80 mg, 0.179 mmol), 4-chlorophenyl boronic acid (30.8 mg, 0.197 mmol), Pd(PPh3)4 (7 mg, 00.006 mmol), saturated sodium bicarbonate (0.64 mL), methanol (1.5 mL), and toluene (0.64 mL) was heated in a microwave reactor for 40 minutes at 110° C. To the solution was added water and ethyl acetate and the two layers were separated. The crude compound was purified by flash column chromatography on silica gel with hexanes and EtOAc (30%) to afford ethyl 3-(4-((5-(4-chlorophenyl)-2,2-dimethyl-2,3-dihydrobenzofuran-7-yl)methoxy)phenyl)-2-methylpropanoate. The ester was dissolved in tetrahydrofuran (1.0 mL), methanol (1.0 mL) and water (3 mL). Lithium hydroxide was added and the reaction was stirred at room temperature for 24 hours. The mixture was acidified with 1M HCl and diluted with EtOAc (3 mL). The organic layer was washed with brine (3 mL), dried over sodium sulfate and filtered. The filtrate was concentrated in vacuo to yield 3-(4-((5-(4-chlorophenyl)-2,2-dimethyl-2,3-dihydrobenzofuran-7-yl)methoxy)phenyl)-2-methylpropanoic acid (111). 1H NMR (400 MHz, CDCl3) δ 7.43-7.39 (m, 3H), 7.34 (d, J=8.3 Hz, 2H), 7.28 (d, J=8.3 Hz, 1H), 7.09 (d, J=8.2 Hz, 2H), 6.94 (d, J=8.3 Hz, 2H), 5.05 (s, 2H), 3.07 (s, 2H), 3.00 (dd, J=13.4, 6.4 Hz, 1H), 2.73-2.67 (m, 1H), 2.62-2.58 (m, 1H), 1.51 (s, 6H), 1.17 (d, J=6.8 Hz, 3H). LC-MS ESI m/z: found 449.1 [M−H]−.

Workup

  1. customthe two layers were separated
  2. customThe crude compound was purified by flash column chromatography on silica gel with hexanes and EtOAc (30%)

Sources & evidence

ORD record
ord-f01c5caff7df45a79ed266d83d9bb6e1
Source dataset
uspto-grants-2012_11
Patent number
US08309600B2

Reaction notes

Loading…