Diisopropylamine → (3-Chlorophenyl)(1-hydroxycyclohexyl)acetic acid

温度

0 °C

A solution of Diisopropylamine (7.87 mL, 56.2 mmol) in dry tetrahydrofuran (50 mL) under nitrogen was cooled to −78° C. and treated dropwise with a solution of n-butyllithium (2.5 M in hexanes, 22 mL, 55.0 mmol). The resulting solution was warmed to 0° C. and stirred for 15 min. The solution was re-cooled to −78° C. and treated, via cannula, with a solution of 3-chlorophenylacetic acid (4.0 g, 23.4 mmol) in tetrahydrofuran (20 mL). The reaction was then allowed to warm to 25° C. where it was stirred for 45 minutes and was then re-cooled to −78° C. A solution of cyclohexanone (3.65 mL, 35.3 mL) in tetrahydrofuran (10 mL) was then added via cannula, and the resulting mixture was stirred at −78° C. for 1.5 h. The reaction was then quenched by the addition of a saturated aqueous solution of ammonium chloride, and the tetrahydrofuran was removed in vacuo. The resulting residue was dissolved in a 2N aqueous solution of sodium hydroxide (30 mL) and washed with ethyl acetate (1×30 mL). The aqueous layer was then acidified to pH=1 with the addition of a 2 N aqueous solution of hydrochloric acid. The product was extracted with ethyl acetate (3×30 mL), and the combined organic extracts were dried over magnesium sulfate and concentrated in vacuo to yield 6.05 g (96%) of pure (3-chlorophenyl)(1-hydroxycyclohexyl)acetic acid as a white solid. HRMS: calcd for C14H17ClO3, 268.0866; found (ESI_FT), 291.0748.

1. temperatureThe solution was re-cooled to −78° C.
2. temperatureto warm to 25° C. where it
3. stirringwas stirred for 45 minutes
4. temperaturewas then re-cooled to −78° C
5. stirringthe resulting mixture was stirred at −78° C. for 1.5 h
6. customThe reaction was then quenched by the addition of a saturated aqueous solution of ammonium chloride
7. customthe tetrahydrofuran was removed in vacuo
8. dissolutionThe resulting residue was dissolved in a 2N aqueous solution of sodium hydroxide (30 mL)
9. washwashed with ethyl acetate (1×30 mL)
10. additionThe aqueous layer was then acidified to pH=1 with the addition of a 2 N aqueous solution of hydrochloric acid
11. extractionThe product was extracted with ethyl acetate (3×30 mL)
12. dry with materialthe combined organic extracts were dried over magnesium sulfate
13. concentrationconcentrated in vacuo

ORDレコード

ord-5920014700ff41d1acc61f40e5b2271c

出典データセット

uspto-grants-2008_09

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US07419980B2