Cyclopentanone → 4-(1-Hydroxycyclopentyl)benzoic acid

Temperature

-78 °C

A solution of 4-bromobenzoic acid (4.02 g, 20.0 mmol) in tetrahydrofuran (100 mL) was purged with argon for 5 min. n-Butyllithium (16.0 mL of 2.5 M in hexanes, 40 mmol) was added dropwise at −78° C., resulting in a yellow thick syrup. The mixture was stirred at −78° C. for 30 min. Cyclopentanone (3.89 mL, 44.0 mmol) was added dropwise. The reaction was quenched immediately with saturated NH4Cl and allowed to warm to room temperature. The mixture was acidified with 1 N HCl to pH ˜3 and extracted with ethyl acetate (3×50 mL). The combined organic layers were washed with brine, dried over MgSO4 and concentrated in vacuo. The solid residue was suspended in hexanes, filtered, and the solid washed with additional hexanes. The solid was re-suspended in dichloromethane followed by hexanes. The resulting precipitate was filtered, washed with hexane and air dried to yield 4-(1-hydroxycyclopentyl)benzoic acid (1.25 g, 30%) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ 12.78 (s, 1H), 7.88 (d, J=8.5 Hz, 2H), 7.58 (d, J=8.5 Hz, 2H), 4.93 (s, 1H), 1.93-1.71 (m, 8H).

1. additionwas added dropwise at −78° C.
2. customresulting in a yellow thick syrup
3. customThe reaction was quenched immediately with saturated NH4Cl
4. temperatureto warm to room temperature
5. extractionextracted with ethyl acetate (3×50 mL)
6. washThe combined organic layers were washed with brine
7. dry with materialdried over MgSO4
8. concentrationconcentrated in vacuo
9. filtrationfiltered
10. washthe solid washed with additional hexanes
11. filtrationThe resulting precipitate was filtered
12. washwashed with hexane and air
13. customdried

ORD record

ord-26460fcf96134848a0933e45c1bef0a1

Source dataset

uspto-grants-2014_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08828996B2