Dimethyl Sulfoxide → (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

HRID 1826151Notes

Reaction equation

HRID 1826151 reaction equation
CS(C)=O.C(Cl)(=O)C(Cl)=O.[CH3:11][C:12]1[C:26]([O:27][CH3:28])=[CH:25][C:15]([C:16]([N:18]2[CH2:22][CH2:21][CH2:20][CH:19]2[CH2:23][OH:24])=[O:17])=[C:14]([NH:29][C:30]([O:32][CH2:33][C:34]([Cl:37])([Cl:36])[Cl:35])=[O:31])[C:13]=1[O:38][CH3:39]>C(Cl)Cl.O>[CH3:11][C:12]1[C:26]([O:27][CH3:28])=[CH:25][C:15]2[C:16](=[O:17])[N:18]3[CH2:22][CH2:21][CH2:20][C@H:19]3[C@H:23]([OH:24])[N:29]([C:30]([O:32][CH2:33][C:34]([Cl:37])([Cl:36])[Cl:35])=[O:31])[C:14]=2[C:13]=1[O:38][CH3:39]

Participants

6

Reactant 3

HCID 679Dimethyl SulfoxideHCID 65578Oxalyl chlorideHCID 53758202HCID 53758202, compound

Product 1

HCID 23574476(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-oneYield 87%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent3×

Procedure

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.

Workup

  1. stirringwas then stirred for a further 45 minutes at −50° C
  2. stirringstirred for a further 15 minutes
  3. waitThe reaction mixture was left
  4. customto separate
  5. washThe organic phase was washed with 1 N HCl (2×50 mL), water (2×50 mL), brine (2×50 mL)
  6. dry with materialdried over MgSO4
  7. customThe solvent was evaporated

Sources & evidence

ORD record
ord-d2ff5240c6494b2dbf0d0e6373c3c859
Source dataset
uspto-grants-2006_05
Patent number
US07049311B1

Reaction notes

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