Reacción #1918169

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′-tri-chloroethoxylcarbonyl)-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°=0 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°=0 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) δ7.05 (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 δ166.82, 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