Acetone → (1R)-1-(3,4-Difluorophenyl)ethan-1-ol

温度

0 °C

(S,R)-cis-1-amino-2-indanol (284.3 mg, 1.91 mmol, 0.1 eq) was dissolved in tetrahydrofuran (25 mL) in a dry two-necked round-bottomed flask fitted with a dropping funnel and nitrogen inlet. The solution was chilled to approximately 0° C. and N,N-diethylaniline-borane complex (3.50 mL, 19.2 mmol, 1 eq) added dropwise. The mixture was allowed to stir at 0° C. for 30 minutes at which time a solution of 3,4-difluoroacetophenone (2.40 mL) in tetrahydrofuran (40 mL) was added via the dropping funnel over approximately 90 minutes. The solution was allowed to slowly warm to room temperature and stirring continued overnight. Acetone (16 mL) was added to the reaction mixture and the solution allowed to stir for a further hour before being concentrated in vacuo. The residue was treated with toluene (100 mL) and washed with 1 M sulphuric acid (4×50 mL), water (2×50 mL) and brine (50 mL). The organic phase was then dried (Na2SO4) and concentrated in vacuo to afford the crude alcohol. Gradient flashmaster chromatography (20 g silica cartridge; 100% petroleum spirits to 100% ethyl acetate) afforded the desired alcohol as a clear oil (2.242 g, 74%).

1. customfitted with a dropping funnel and nitrogen inlet
2. additionN,N-diethylaniline-borane complex (3.50 mL, 19.2 mmol, 1 eq) added dropwise
3. additionwas added via the dropping funnel over approximately 90 minutes
4. temperatureto slowly warm to room temperature
5. stirringto stir for a further hour
6. concentrationbefore being concentrated in vacuo
7. additionThe residue was treated with toluene (100 mL)
8. washwashed with 1 M sulphuric acid (4×50 mL), water (2×50 mL) and brine (50 mL)
9. dry with materialThe organic phase was then dried (Na2SO4)
10. concentrationconcentrated in vacuo
11. customto afford the crude alcohol

ORDレコード

ord-edfdf116461d4c088d8ebc3aff2c9fa6

出典データセット

uspto-grants-2010_06

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US07737143B2