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

Temperature

50 °C

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.

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)

ORD record

ord-c7e205ac620a427b881a46b8ec5de9f8

Source dataset

uspto-grants-2011_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07906653B2