Sodium hydride → HCID 18672411, compound

Temperature

-78 °C

A solution of 5-chloro-2-iodobenzylalcohol (0.948 g, 3.53 mmol) in dry THF (27 mL) was added, rinsing with dry THF, to a stirred suspension of NaH (0.155 g, 3.89 mmol) in dry THF (9 mL) at 0° C. After 5 min the mixture was cooled to −78° C. and n-butyl-lithium (2.5 M in hexanes, 2.97 mL, 7 mmol) was added dropwise over 5 minutes. After a further 10 min, a solution of N-(2,2-difluoroethylidene)-N-(4-methoxyphenyl)amine (0.654 g, 3.53 mmol) in dry THF (9 mL) was added. After 1 h the mixture was quenched with excess saturated aqueous NH4Cl at −78° C. then was stirred at ambient temperature for 15 min. The solution was partitioned between EtOAc and brine. The EtOAc layer was dried (Na2SO4) and evaporated in vacuo and the residue was purified by flash column chromatography on silica (eluting with 5% methylene chloride, 5-30% ethyl acetate/hexanes gradient) to give (5-chloro-2-{2,2-difluoro-1-[(4-methoxyphenyl)amino]ethyl}phenyl)methanol (0.439 g) as an oil: MS 328.4 (M+1); 1H NMR (CDCl3, 400 MHz) δ 2.00 (br s, 1H), 3.70 (s, 3H), 4.14 (br s, 1H), 4.82 (m, 2H), 5.02 (m, 1H), 6.08 (dt, J=3.0 Hz, 56.0 Hz, 1H), 6.57 (d, J=9.0 Hz, 2H), 6.71 (d, J=9.0 Hz), 2H), 7.29 (dd, J=2.2 and 8.4 Hz, 1H), 7.40 (d, J=2.2 Hz, 1H), 7.47 (d, J=8.4 Hz, 1H).

1. customAfter 1 h the mixture was quenched with excess saturated aqueous NH4Cl at −78° C.
2. customThe solution was partitioned between EtOAc and brine
3. dry with materialThe EtOAc layer was dried (Na2SO4)
4. customevaporated in vacuo
5. customthe residue was purified by flash column chromatography on silica (eluting with 5% methylene chloride, 5-30% ethyl acetate/hexanes gradient)

ORD record

ord-0a3b976d9bb343e393c1f84fc9d2be13

Source dataset

uspto-grants-2003_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06515011B2