Hydrochloric Acid → HCID 89519566, compound

Participants

Reaction Conditions

Reaction Steps

Weinreb amide 76 (0.33 g, 1.08 mmol) was dissolved in THF (15 mL), put under an argon atmosphere and cooled to 0° C. LiAlH4 (1.5 eq., 1.68 mmol, 1.68 mL of a 1 M solution in THF) was added slowly and the mixture was stirred at 0° C. for 1 hour after which TLC analysis indicated complete conversion of the starting compound. 0.1 M aq. HCl (1 mL) was slowly added and the mixture was stirred vigorously for 5 minutes. The organic layer was extracted with sat. aq. NaHCO3 (2×) and brine, dried over MgSO4 and concentrated under reduced pressure. Diethyl ((methylsulfonyl)methyl)phosphonate (1.5 eq., 1.68 mmol, 0.39 g) was dissolved in THF (20 mL) and cooled to 0° C. under an argon atmosphere. NaH (1.3 eq., 1.46 mmol, 58.0 mg, 60% w/w in mineral oil) was slowly added and the mixture was stirred at 0° C. for 30 minutes. Next, the freshly obtained aldehyde (in THF (2 mL)) was slowly added and the mixture was stirred for 2 hours while slowly warming it to room temperature. After this time, TLC analysis indicated complete conversion of the aldehyde. The reaction was quenched by addition of 1 M aq. HCl (1 mL) after which the mixture was diluted with EtOAc and extracted with sat. aq. NaHCO3 (2×) and brine, dried over MgSO4 and concentrated under reduced pressure. The title compound was obtained after column chromatography (40%->80% Acetone/PE) as a colorless solid (yield: 117 mg, 0.36 mmol, 32%). 1H NMR (400 MHz, CDCl3): δ=8.50 (d, J=5.28 Hz, 2H), 7.15 (d, J=5.90 Hz, 2H), 6.92 (dd, J=15.10, 4.76 Hz, 1H), 6.53 (d, J=15.10 Hz, 1H), 5.56 (d, J=8.99 Hz, 1H), 4.80-4.72 (m, 1H), 3.02-2.84 (m, 2H), 2.93 (s, 3H), 1.39 (s, 9H) ppm. 13C NMR (100 MHz, CDCl3): δ=154.87, 149.59, 146.40, 145.41, 130.04, 124.51, 80.10, 51.10, 42.58, 39.48, 28.06 ppm. [α]D23=−6.0 (c=1, MeOH). HRMS: calcd. for C15H22N2O4S [M+H]+327.13730. found 327.13741.

Provenance & Evidence