Dimethyl Sulfoxide → HCID 20664169, compound

Temperature

-78 °C

Dimethylsulfoxide (0.121 mL, 1.7 mmol) was added to a solution of oxalyl chloride (0.07 mL, 0.8 mmol) in 10 mL of CH2Cl2 at −78° C. under nitrogen. The reaction mixture was stirred at −78° C. for 20 min., then a solution of dihydro-3-(R)-(3-(R)-(hydroxymethyl)-4-(S)-(3-fluorophenyl)-pyrrolidin-1-yl)-4,4-dimethyl-2(3H)furanone (200 mg, 0.65 mmol) in 1 mL of CH2Cl2 was added. The mixture was stirred at −78° C. for an additional 45 min., then triethylamine (0.46 mL, 3.3 mmol) was added and the cold bath was removed. After the reaction mixture had warmed to room temperature, it was diluted with CH2Cl2 and washed with 1N NaOH and brine. The solution was dried over Na2SO4, filtered and concentrated to afford 100 mg (50% yield) of the title compound. 1H NMR (400 MHz, CDCl3). δ1.17 (s, 3H), 1.24 (s, 3H), 3.08-3.24 (m, 4H), 3.35 (t, 1H, J=8.4 Hz), 3.55 (dd, 1H, J=5.9, 9.6 Hz), 3.66 (dd, 1H, J=7.9, 16 Hz), 3.91 (d, 1H, J=9.0 Hz), 3.98 (d, 1H, J=9.0 Hz), 6.95-6.97 (m, 1H), 7.04 (dt, 1H, J=2.1, 10 Hz), 7.10 (d, 1H, J=7.8 Hz), 7.27-7.32 (m, 1H), 9.71 (d, 1H, J=2.0 Hz). ESI-MS. M/z; (M+H)=306.2.

1. stirringThe mixture was stirred at −78° C. for an additional 45 min.
2. customthe cold bath was removed
3. temperatureAfter the reaction mixture had warmed to room temperature
4. additionit was diluted with CH2Cl2
5. washwashed with 1N NaOH and brine
6. dry with materialThe solution was dried over Na2SO4
7. filtrationfiltered
8. concentrationconcentrated

ORD record

ord-360f74b6aada44ce8c8aeb975dc03168

Source dataset

uspto-grants-2001_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06248755B1