1,2-Dichloroethane → HCID 86679551, compound

HRID 1776599Notes

Reaction equation

HRID 1776599 reaction equation
FC(F)(F)C([O-])=O.[C:8]([CH2:11][S:12][C:13]([C:15]1[CH:16]=[CH:17][C:18]([O:34][CH3:35])=[C:19]([N:21]([CH2:26][CH2:27][NH+:28]2[CH2:33][CH2:32][O:31][CH2:30][CH2:29]2)[S:22]([CH3:25])(=[O:24])=[O:23])[CH:20]=1)=[O:14])([OH:10])=[O:9].[Cl:36][C:37]1[CH:38]=[N+:39]([O-:62])[CH:40]=[C:41]([Cl:61])[C:42]=1[CH2:43][C@@H:44]([C:46]1[CH:51]=[CH:50][C:49]([O:52][CH:53]([F:55])[F:54])=[C:48]([O:56][CH2:57][CH:58]2[CH2:60][CH2:59]2)[CH:47]=1)O.C(Cl)CCl>C(Cl)Cl.CN(C1C=CN=CC=1)C>[ClH:36].[Cl:36][C:37]1[CH:38]=[N+:39]([O-:62])[CH:40]=[C:41]([Cl:61])[C:42]=1[CH2:43][C@@H:44]([C:46]1[CH:51]=[CH:50][C:49]([O:52][CH:53]([F:55])[F:54])=[C:48]([O:56][CH2:57][CH:58]2[CH2:60][CH2:59]2)[CH:47]=1)[O:9][C:8](=[O:10])[CH2:11][S:12][C:13](=[O:14])[C:15]1[CH:16]=[CH:17][C:18]([O:34][CH3:35])=[C:19]([N:21]([CH2:26][CH2:27][N:28]2[CH2:33][CH2:32][O:31][CH2:30][CH2:29]2)[S:22]([CH3:25])(=[O:24])=[O:23])[CH:20]=1

Participants

6

Reactant 3

HCID 111,2-DichloroethaneHCID 71092687HCID 71092687, compoundHCID 86679553HCID 86679553, compound

Product 1

HCID 86679551HCID 86679551, compoundYield 86.4%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent2×

Procedure

4-(2-(N-(5-((carboxymethylthio)carbonyl)-2-methoxyphenyl)-methylsulfonamido)-ethyl)morpholin-4-ium 2,2,2-trifluoroacetate (0.194 g, 0.355 mmol) was suspended in dry DCM (3.5 ml), and (S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-hydroxyethyl)pyridine 1-oxide (0.115 g, 0.273 mmol), EDC (0.157 g, 0.819 mmol), and DMAP (0.0667 g, 0.546 mmol) were sequentially added with stirring at RT under nitrogen. The resulting yellow solution was stirred at the same temperature for 24 hours. The mixture was diluted with DCM and washed twice with 1N HCl and then with brine. The organic phase was dried over Na2SO4, and the solvent was removed under vacuum. The crude was purified by flash chromatography on silica gel column (DCM:MeOH=96:4) followed by preparative HPLC under neutral conditions. The fraction obtained after solvent evaporation was dissolved in Et2O and HCl in Et2O was added; the resulting suspension was stirred at RT for few minutes. The volatiles were removed, and the residue was dried affording (S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-(2-(4-methoxy-3-(N-(2-morpholinoethyl)-methylsulfonamido)benzoylthio)acetoxy)-ethyl)pyridine 1-oxide hydrochloride (0.103 g, 0.118 mmol, 43.3% yield, LC-MS purity (BPI): 99.7%, MS/ESI+ 834.34 [MH]+, [αD]=−54.00, c=0.5, MeOH).

Workup

  1. stirringThe resulting yellow solution was stirred at the same temperature for 24 hours
  2. washwashed twice with 1N HCl
  3. dry with materialThe organic phase was dried over Na2SO4
  4. customthe solvent was removed under vacuum
  5. customThe crude was purified by flash chromatography on silica gel column (DCM:MeOH=96:4)
  6. customThe fraction obtained
  7. customafter solvent evaporation
  8. dissolutionwas dissolved in Et2O
  9. additionHCl in Et2O was added
  10. stirringthe resulting suspension was stirred at RT for few minutes
  11. customThe volatiles were removed
  12. customthe residue was dried

Sources & evidence

ORD record
ord-a66cf516de334d28a2da55ea791966af
Source dataset
uspto-grants-2016_02
Patent number
US09265768B2

Reaction notes

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