2-Bromothiophene → HCID 95003689, compound

To a solution of 2-bromothiophene (0.95 mL, 9 mmol) in ether (60 mL) cooled to −100° C. was added t-butyl lithium (5.41 mL of 1.7 M in pentane, 9 mmol) by dropwise addition. The reaction mixture was stirred at this temperature for 30 min. (R)-Epichlorohydrin (1.08 mL, 14 mmol) was added and the −100° C. bath was replaced with an ice/ethanol bath. The reaction was stirred at this temperature for 1.5 h and then stirred in an ice-bath for an additional 1.5 h. The reaction mixture was poured onto water and extracted with EtOAc (3 times). The combined organic phases were washed with brine, dried over MgSO4 and concentrated. The residue was purified by flash chromatography (50% EtOAc in heptane eluent) to afford (R)-1-chloro-3-thiophen-2-yl-propan-2-ol (410 mg, 25%) as a brown oil. 1H NMR (300 MHz, CHLOROFORM-d) δ ppm 2.28 (d, J=4.14 Hz, 1H) 3.06-3.21 (m, 2H) 3.46-3.73 (m, 2H) 4.08 (d, J=5.65 Hz, 1H) 6.91 (dd, J=3.39, 0.94 Hz, 1H) 6.98 (dd, J=5.09, 3.39 Hz, 1H) 7.21 (dd, J=5.18, 1.22 Hz, 1H).

1. additionby dropwise addition
2. additionwas added
3. customthe −100° C. bath was replaced with an ice/ethanol bath
4. stirringstirred in an ice-bath for an additional 1.5 h
5. additionThe reaction mixture was poured onto water
6. extractionextracted with EtOAc (3 times)
7. washThe combined organic phases were washed with brine
8. dry with materialdried over MgSO4
9. concentrationconcentrated
10. customThe residue was purified by flash chromatography (50% EtOAc in heptane eluent)

ORD record

ord-3629536852bd48d486c45d8123b98d6d

Source dataset

uspto-grants-2016_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09353096B2