Hydrochloric Acid → HCID 57835856, compound

HRID 731179Notes

Reaction equation

HRID 731179 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:9]([C:16]2[CH:21]=[CH:20][C:19]([O:22][CH:23]3[CH2:31][C:30]4[C:25](=[CH:26][CH:27]=[CH:28][CH:29]=4)[CH2:24]3)=[CH:18][CH:17]=2)[CH2:10][C:11]([O:13]CC)=[O:12])[CH:5]=[C:6]([F:8])[CH:7]=1.[Li+].[OH-].Cl>C1COCC1.C(O)C.O>[F:1][C:2]1[CH:3]=[C:4]([CH:9]([C:16]2[CH:17]=[CH:18][C:19]([O:22][CH:23]3[CH2:31][C:30]4[C:25](=[CH:26][CH:27]=[CH:28][CH:29]=4)[CH2:24]3)=[CH:20][CH:21]=2)[CH2:10][C:11]([OH:13])=[O:12])[CH:5]=[C:6]([F:8])[CH:7]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 3939Lithium HydroxideHCID 57835859HCID 57835859, compound

Product 1

HCID 57835856HCID 57835856, compound

Reagents, catalysts & solvents 1

HCID 18504229Ethanol tetrahydrofuran waterSolvent

Procedure

(+/−)3-(3,5-Difluoro-phenyl)-3-[4-(indan-2-yloxy)-phenyl]-propionic acid ethyl ester 35 (25 mg) was dissolved in 3 mL THF-EtOH-H2O (1/1/1), and LiOH (20 mg) was added. The mixture was stirred at room temperature for 6 hours. 1N HCl was added to acidify the mixture to pH 2-3. The mixture was extracted with EtOAc (2×20 mL). The organic solution was washed with water and brine, dried over Na2SO4, concentrated, and flash chromatographed (0-60% EtOAc in hexane). (+/−)-3-(3,5-Difluorophenyl)-3-(4-(2,3-dihydro-1H-inden-2-yloxy)phenyl) propanoic acid 36 was obtained as a colorless oil. MS ESI (neg.) m/e: 393 (M−H). 1H NMR (500 MHz) (CDCl3) δ 7.25-7.31 (m, 2H); 7.20-7.22 (m, 2H); 7.14 (d, J =8.4 Hz, 2H); 6.87 (d, J=8.4 Hz, 2H); 6.78 (d, J =6.5 Hz, 2H); 6.67 (t, J =8.9 Hz, 1H); 5.16 (m, 1H); 4.47 (t, J=7.8 Hz, 1H); 3.38 (dd, J =16.7, 6.3 Hz, 2H); 3.19 (dd, J=16.7, 2.6 Hz, 2H); 3.06 (d, J =7.9 Hz, 2H).

Workup

  1. extractionThe mixture was extracted with EtOAc (2×20 mL)
  2. washThe organic solution was washed with water and brine
  3. dry with materialdried over Na2SO4
  4. concentrationconcentrated
  5. customflash chromatographed (0-60% EtOAc in hexane)

Sources & evidence

ORD record
ord-ea297380233147ee8ad08e085dead1a7
Source dataset
uspto-grants-2009_09
Patent number
US07582803B2

Reaction notes

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