Water → 2,2-Dimethyl-1-[5-(trifluoromethyl)-1,3-benzothiazol-2-yl]-1-propanol

Temperature

-78 °C

To a stirred solution of 3.8 g (19.0 mmol) of 5-(trifluoromethyl)-1,3-benzothiazole in 30 mL of tetrahydrofuran at −78° C. was added 13.1 mL (21.0 mmol) of a 1.6 M solution of n-butyllithium in hexane over 45 min. Then, 1.8 g (21.0 mmol) of trimethylacetaldehyde in 10 mL of tetrahydrofuran was added dropwise over 30 min. The reaction mixture was stirred for 1 h at −78° C., and then allowed to warm to 0° C. Then, 25 mL of water was added and the mixture was extracted with 80 mL of ether. The ether was washed with 40 mL of water (3×), dried over anhydrous magnesium sulfate, and concentrated in vacuo. The residue was purified by silica gel chromatography eluting with ethyl acetate:hexane (1:9) to afford 1.8 g (33%) of 2,2-dimethyl-1-[5-(trifluoromethyl)-1,3-benzothiazol-2-yl]-1-propanol as an off-white solid. The enantiomers were separated in 98.8% ee using a Chiralpak AD, 10 micron column with a mobile phase of 90% carbon dioxide: 10% methanol and a flow rate of 2.0 mL/minute. 1H-NMR (400MHz, DMSO-d6): δ 8.33–8.29 (m, 2H), 7.71 (d, J=8 Hz, 1H), 6.61 (d, J=5 Hz, 1H), 4.60 (d, J=5 Hz, 1H), 0.97 (s, 9H).

1. temperatureto warm to 0° C
2. extractionthe mixture was extracted with 80 mL of ether
3. washThe ether was washed with 40 mL of water (3×)
4. dry with materialdried over anhydrous magnesium sulfate
5. concentrationconcentrated in vacuo
6. customThe residue was purified by silica gel chromatography
7. washeluting with ethyl acetate:hexane (1:9)

ORD record

ord-013c4537b18e43b3b1829c120c69e52b

Source dataset

uspto-grants-2007_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07288541B2