Dimethyl Sulfoxide → HCID 68008509, compound

HRID 1429070Notes

Reaction equation

HRID 1429070 reaction equation
C(Cl)(=O)C(Cl)=O.CS(C)=O.[C:11]([O:19][C@@H:20]1[CH2:54][N:23]2[C:24](=[O:53])[C@@H:25]([NH:45][C:46]([O:48][C:49]([CH3:52])([CH3:51])[CH3:50])=[O:47])[CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][C@H:31]([OH:44])[CH2:32][C@@H:33]3[CH2:38][C@@:34]3([C:39]([O:41][CH2:42][CH3:43])=[O:40])[NH:35][C:36](=[O:37])[C@@H:22]2[CH2:21]1)(=[O:18])[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.C(N(CC)CC)C>ClCCl>[C:11]([O:19][C@@H:20]1[CH2:54][N:23]2[C:24](=[O:53])[C@@H:25]([NH:45][C:46]([O:48][C:49]([CH3:51])([CH3:50])[CH3:52])=[O:47])[CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][C:31](=[O:44])[CH2:32][C@@H:33]3[CH2:38][C@@:34]3([C:39]([O:41][CH2:42][CH3:43])=[O:40])[NH:35][C:36](=[O:37])[C@@H:22]2[CH2:21]1)(=[O:18])[C:12]1[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=1

Participants

6

Reactant 4

HCID 679Dimethyl SulfoxideHCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 68009002HCID 68009002, compound

Product 1

HCID 68008509HCID 68008509, compoundYield 84.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of oxalyl chloride (0.092 ml, 1.05 mmol) in dichloromethane (1.75 ml) at −78° C. was added dropwise DMSO (0.149 ml, 2.10 mmol). The reaction mixture was stirred for 10 min and then a solution of (2S,6S,12S,13aS,14aR,16aS)-ethyl 2-(benzoyloxy)-6-(tert-butoxycarbonylamino)-12-hydroxy-5,16-dioxooctadecahydrocyclopropa[e]pyrrolo[1,2-a][1,4]diazacyclopentadecine-14a-carboxylate (Example 1b, 0.43 g, 0.698 mmol) in dichloromethane (4 ml) was added dropwise. The reaction mixture was stirred at −78° C. for 30 min and triethylamine (0.730 ml, 5.24 mmol) was added dropwise. The reaction mixture was stirred at −78° C. for 15 min and warmed to room temperature and stirred for 1.5 hr. The reaction mixture was quenched with water, stirred for 30 min and extracted with dichloromethane and the organic layer dried over anhydrous sodium sulfate, filtered, and evaporated under reduced pressure. The residue was purified by flash chromatography on silica gel (dichloromethane/methanol=40/1) to provide the title compound (2S,6S,13aS,14aR,16aS)-ethyl 2-(benzoyloxy)-6-(tert-butoxycarbonylamino)-5,12,16-trioxooctadecahydrocyclopropa[e]pyrrolo[1,2-a][1,4]diazacyclopentadecine-14a-carboxylate (0.36 g, 0.59 mmol, 84% yield).

Workup

  1. stirringThe reaction mixture was stirred at −78° C. for 30 min
  2. stirringThe reaction mixture was stirred at −78° C. for 15 min
  3. stirringstirred for 1.5 hr
  4. customThe reaction mixture was quenched with water
  5. stirringstirred for 30 min
  6. extractionextracted with dichloromethane
  7. dry with materialthe organic layer dried over anhydrous sodium sulfate
  8. filtrationfiltered
  9. customevaporated under reduced pressure
  10. customThe residue was purified by flash chromatography on silica gel (dichloromethane/methanol=40/1)

Sources & evidence

ORD record
ord-a029ead7506145c786771d3a2be48732
Source dataset
uspto-grants-2015_01
Patent number
US08937041B2

Reaction notes

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