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 1830987Notes

Reaction equation

HRID 1830987 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°=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.

Workup

  1. stirringwas then stirred for a further 45 minutes at −50°=0 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-32e4fd27afb3474d8de094ecc0973ae0
Source dataset
uspto-grants-2006_06
Patent number
US07067511B2

Reaction notes

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