Reacción #1913333

Ecuación de reacción

192

N-(4-Methyl-3,5-dimethoxy-2-[trichloroethyloxycarbonylamino]-benzoyl) pyrrolidine-2-methanol

DMSO

oxalyl chloride

→

product ( 193 )

Rendimiento 87.0%

(11S,11aS)-8-Methyl-7,9-dimethoxy-11-hydroxy-10-N-(2′,2′,2′-trichloroethoxylcarbonyl)-1,2,3,10,11,11a-hexahydro-5H-pyrrolo[2,1-c][1,4] benzodiazepin-5-one

Rendimiento 87.0%

Disolventes

DCM

H2O

DCM

DCM

Condiciones de reacción

Tratamiento posterior

1. 1
   workup.STIRRINGwas then stirred for a further 45 minutes at −50° C
2. 2
   workup.STIRRINGstirred for a further 15 minutes
3. 3
   workup.WAITThe reaction mixture was left
4. 4
   Otroto separate
5. 5
   LavadoThe organic phase was washed with 1 N HCl (2×50 mL), water (2×50 mL), brine (2×50 mL)
6. 6
   Secadodried over MgSO4
7. 7
   OtroThe solvent was evaporated

Procedimiento

Anhydrous DMSO (1.006 g, 12.87 mmol) in dry DCM (10 mL) was added dropwise over 5 minutes to a stirred solution of oxalyl chloride (3.19 mL of a 2 N solution in DCM, 6.373 mmol) under a nitrogen atmosphere at −50° C. After stirring for 5 minutes, a solution of 192 (2.13 g, 4.53 mmol) in dry DCM (10 mL) was added dropwise over 45 minutes to the reaction mixture, which was then stirred for a further 45 minutes at −50° C. TEA (1.83 g; 18.13 mmol) was added dropwise to the mixture over 0.5 hours and stirred for a further 15 minutes. The reaction mixture was left to warm to room temperature, diluted with H2O (100 ml) and the phases allowed to separate. The organic phase was washed with 1 N HCl (2×50 mL), water (2×50 mL), brine (2×50 mL) and dried over MgSO4. The solvent was evaporated to afford the product (193) as an off-white glass (1.84 g, 3.93 mmol; 87%). 1H NMR (270 MHz, CDCl3) δ 7.05 (s, 1H) (minor rotamer 1:4, visible at d 7.06), 5.58 (dd, J=3.84 Hz, J=9.89, 1H) (minor rotamer 1:4, visible at d 5.68, J=4.21 Hz, J=9.53), 4.71 (d, J=11.72 Hz, 1H), 4.56 (d, J=11.73 Hz, 1H), 4.11 (d, J=3.85 Hz, 1H), 3.88 (s, 3H), 3.76 (s, 3H), 3.79-3.47 (m, 2H), 2.21-1.99 (m, 4H), 2.16 (s, 3H); 13C NMR (67.8 MHz, CDCl3) rotamers δ 166.82, 158.31, 157.92, 155.65, 155.43, 131.52, 124.17, 123.99, 121.62, 105.90, 105.64, 105.38, 94.53, 86.17, 85.93, 75.80, 75.23, 61.77, 61.65, 59.98, 59.58, 59.40, 55.88, 55.79, 46.56, 46.38, 28.70, 28.62, 22.94, 10.14, 9.75.

Fuente