Hydrochloric Acid → HCID 58566337, compound

HRID 1909603Notes

Reaction equation

HRID 1909603 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:9]=[C:10]([CH2:19][O:20][C:21]3[CH:26]=[CH:25][C:24]([CH2:27][CH:28]([CH3:34])[C:29]([O:31]CC)=[O:30])=[CH:23][CH:22]=3)[C:11]3[O:15][C:14]([CH3:17])([CH3:16])[CH2:13][C:12]=3[CH:18]=2)=[CH:4][CH:3]=1.CO.[OH-].[Li+].Cl>O1CCCC1.CCOC(C)=O.O>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[CH:9]=[C:10]([CH2:19][O:20][C:21]3[CH:22]=[CH:23][C:24]([CH2:27][CH:28]([CH3:34])[C:29]([OH:31])=[O:30])=[CH:25][CH:26]=3)[C:11]3[O:15][C:14]([CH3:17])([CH3:16])[CH2:13][C:12]=3[CH:18]=2)=[CH:6][CH:7]=1

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 887MethanolHCID 3939Lithium HydroxideHCID 67406232Ethyl 3-(4-((5-(4-chlorophenyl)-2,2-dimethyl-2,3-dihydrobenzofuran-7-yl)methoxy)phenyl)-2-methylpropanoate

Product 1

HCID 58566337HCID 58566337, compound

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

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. washThe organic layer was washed with brine (3 mL)
  2. dry with materialdried over sodium sulfate
  3. filtrationfiltered
  4. concentrationThe filtrate was concentrated in vacuo

Sources & evidence

ORD record
ord-394d5176f69a47d28d0bd0e4ad6c7720
Source dataset
uspto-grants-2013_12
Patent number
US08598374B2

Reaction notes

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