Lithium Hydroxide → ((1S)-5-{3-[2-methoxy-4-(3-thienyl)phenoxy]propoxy}-2,3-dihydro-1H-inden-1-yl)acetic acid

HRID 603414Notes

Reaction equation

HRID 603414 reaction equation
[CH3:1][O:2][C:3]1[CH:28]=[C:27]([C:29]2[CH:33]=[CH:32][S:31][CH:30]=2)[CH:26]=[CH:25][C:4]=1[O:5][CH2:6][CH2:7][CH2:8][O:9][C:10]1[CH:11]=[C:12]2[C:16](=[CH:17][CH:18]=1)[C@H:15]([CH2:19][C:20]([O:22]CC)=[O:21])[CH2:14][CH2:13]2.[Li+].[OH-]>CCO.C1COCC1.O>[CH3:1][O:2][C:3]1[CH:28]=[C:27]([C:29]2[CH:33]=[CH:32][S:31][CH:30]=2)[CH:26]=[CH:25][C:4]=1[O:5][CH2:6][CH2:7][CH2:8][O:9][C:10]1[CH:11]=[C:12]2[C:16](=[CH:17][CH:18]=1)[C@H:15]([CH2:19][C:20]([OH:22])=[O:21])[CH2:14][CH2:13]2

Participants

6

Reactant 2

HCID 3939Lithium HydroxideHCID 59300464ethyl ((1S)-5-{3-[2-methoxy-4-(3-thienyl)phenoxy]propoxy}-2,3-dihydro-1H-inden-1-yl)acetate

Product 1

HCID 59300514((1S)-5-{3-[2-methoxy-4-(3-thienyl)phenoxy]propoxy}-2,3-dihydro-1H-inden-1-yl)acetic acidYield 76%

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
50 °C

Procedure

The ester prepared in Example 98 (83 mg 0.18 mmol) was dissolved in a mixture of EtOH (3 mL), THF (3 mL), and water (1 mL), LiOH (42.6 mg, 1.78 mmol) was added and the reaction mixture was heated at 50° C. for 3 h. The reaction mixture was concentrated under reduced pressure, diluted with water, and extracted with EtOAc. The combined organic phases were dried over MgSO4, filtered, and concentrated under reduced pressure. The crude material was purified by preparative HPLC (CH3CN, 0.01% TFA/Water, 0.01% TFA (v/v)=2:3 to 100% CH3CN, 0.01% TFA) to give 60 mg (73%) of the title compound as a white solid. 1H NMR (400 MHz, acetone-d6): δ 7.62-7.61 (m, 1H), 7.52-7.47 (m, 2H), 7.29 (d, 1H), 7.23-7.20 (m, 1H), 7.14 (d, 1H), 7.01 (d, 1H), 6.33-6.32 (m, 1H), 6.77-6.74 (m, 1H), 4.23-4.18 (m, 4H), 3.89 (s, 3H), 3.48-3.45 (m, 1H), 3.22-2.71 (b, 1H), 2.93-2.71 (m, 3H), 2.42-2.32 (m, 2H), 2.28-2.22 (q, 2H), 1.76-1.70 (m, 1H). LC-MS: RT=5.28 min, (M−H) 437.3.

Workup

  1. additionwas added
  2. concentrationThe reaction mixture was concentrated under reduced pressure
  3. additiondiluted with water
  4. extractionextracted with EtOAc
  5. dry with materialThe combined organic phases were dried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe crude material was purified by preparative HPLC (CH3CN, 0.01% TFA/Water, 0.01% TFA (v/v)=2:3 to 100% CH3CN, 0.01% TFA)

Sources & evidence

ORD record
ord-c7e205ac620a427b881a46b8ec5de9f8
Source dataset
uspto-grants-2011_03
Patent number
US07906653B2

Reaction notes

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