Hydrochloric Acid → 3-(4-((5-(Diethylamino)-2,2-dimethyl-2,3-dihydrobenzofuran-7-yl)methoxy)phenyl)-2-methylpropanoic acid

HRID 1909605Notes

Reaction equation

HRID 1909605 reaction equation
[CH2:1]([N:3]([CH2:31][CH3:32])[C:4]1[CH:5]=[C:6]([CH2:15][O:16][C:17]2[CH:22]=[CH:21][C:20]([CH2:23][CH:24]([CH3:30])[C:25]([O:27]CC)=[O:26])=[CH:19][CH:18]=2)[C:7]2[O:11][C:10]([CH3:13])([CH3:12])[CH2:9][C:8]=2[CH:14]=1)[CH3:2].CO.[OH-].[Li+].Cl>O1CCCC1.CCOC(C)=O.O>[CH2:31]([N:3]([CH2:1][CH3:2])[C:4]1[CH:5]=[C:6]([CH2:15][O:16][C:17]2[CH:18]=[CH:19][C:20]([CH2:23][CH:24]([CH3:30])[C:25]([OH:27])=[O:26])=[CH:21][CH:22]=2)[C:7]2[O:11][C:10]([CH3:12])([CH3:13])[CH2:9][C:8]=2[CH:14]=1)[CH3:32]

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 887MethanolHCID 3939Lithium HydroxideHCID 67405352Ethyl 3-(4-((5-(diethylamino)-2,2-dimethyl-2,3-dihydrobenzofuran-7-yl)methoxy)phenyl)-2-methylpropanoate

Product 1

HCID 468369663-(4-((5-(Diethylamino)-2,2-dimethyl-2,3-dihydrobenzofuran-7-yl)methoxy)phenyl)-2-methylpropanoic acid

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of ethyl 3-(4-((5-bromo-2,2-dimethyl-2,3-dihydrobenzofuran-7-yl)methoxy)phenyl)-2-methylpropanoate (110) (78 mg, 0.17 mmol), diethylamine (0.08 mL, 0.78 mmol), [1,1′-biphenyl]-2-yldi-tert-butylphosphine (16 mg, 0.052 mmol), tris(dibenzylideneacetone)dipalladium (47.6 mg, 0.052 mmol), and sodium t-butoxide (25 mg, 0.26 mmol) in toluene (2 mL) was heated in a pressure tube at 80° C. overnight. Water was added and the reaction was extracted with ethyl acetate and the combined organic layers dried over sodium sulfate, filtered and concentrated in vacuo. The crude compound was purified by flash column chromatography on silica gel with hexanes and EtOAc (50%) to give ethyl 3-(4-((5-(diethylamino)-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-(diethylamino)-2,2-dimethyl-2,3-dihydrobenzofuran-7-yl)methoxy)phenyl)-2-methylpropanoic acid (118). 1H NMR (400 MHz, CDCl3) δ 7.38 (s, 1H), 7.18 (s, 1H), 7.09 (d, J=8.1 Hz, 2H), 6.87 (d, J=8.3 Hz, 2H), 5.04 (s, 2H), 3.84-3.47 (m, 2H), 3.34-3.09 (m, 2H), 3.06 (s, 2H), 3.01-2.89 (m, 1H), 2.78-2.57 (m, 2H), 1.51 (s, 6H), 1.18 (d, J=6.7 Hz, 3H), 1.07 (t, J=6.9 Hz, 6H). LC-MS ESI m/z: found 410.4 [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-4112d3ca76104a98929dfe655ba17c0d
Source dataset
uspto-grants-2013_12
Patent number
US08598374B2

Reaction notes

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