1,4-Dioxane → HCID 71543017, compound

HRID 1776593Notes

Reaction equation

HRID 1776593 reaction equation
C(OC([N:8]([C:13]1[CH:51]=[CH:50][C:16]([C:17]([S:19][CH2:20][C:21]([O:23][C@H:24]([C:35]2[CH:40]=[CH:39][C:38]([O:41][CH:42]([F:44])[F:43])=[C:37]([O:45][CH2:46][CH:47]3[CH2:49][CH2:48]3)[CH:36]=2)[CH2:25][C:26]2[C:31]([Cl:32])=[CH:30][N+:29]([O-:33])=[CH:28][C:27]=2[Cl:34])=[O:22])=[O:18])=[CH:15][C:14]=1[O:52][CH2:53][CH:54]1[CH2:56][CH2:55]1)[S:9]([CH3:12])(=[O:11])=[O:10])=O)(C)(C)C.O1CCOCC1>C(Cl)Cl.Cl>[Cl:34][C:27]1[CH:28]=[N+:29]([O-:33])[CH:30]=[C:31]([Cl:32])[C:26]=1[CH2:25][C@@H:24]([C:35]1[CH:40]=[CH:39][C:38]([O:41][CH:42]([F:43])[F:44])=[C:37]([O:45][CH2:46][CH:47]2[CH2:49][CH2:48]2)[CH:36]=1)[O:23][C:21](=[O:22])[CH2:20][S:19][C:17](=[O:18])[C:16]1[CH:50]=[CH:51][C:13]([NH:8][S:9]([CH3:12])(=[O:11])=[O:10])=[C:14]([O:52][CH2:53][CH:54]2[CH2:55][CH2:56]2)[CH:15]=1

Participants

5

Reactant 2

HCID 312751,4-Dioxane2×HCID 89455839HCID 89455839, compound

Product 1

HCID 71543017HCID 71543017, compoundYield 79%

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidSolvent2×HCID 6344DichloromethaneSolvent

Procedure

To a solution of (S)-4-(2-(2-(4-(N-(tert-butoxycarbonyl)methylsulfonamido)-3-(cyclopropylmethoxy)benzoylthio)acetoxy)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)ethyl)-3,5-dichloropyridine 1-oxide (0.046 g, 0.053 mmol) in DCM (2 ml), HCl 4M in dioxane (0.013 ml, 0.053 mmol) was added and the resulting mixture was stirred at RT overnight. Three more additions of HCl 4M in dioxane (0.265 ml, 1.06 mmol) over five days were performed. The volatiles were removed under vacuum and the crude was purified by filtration through a silica gel cartridge (DCM:Et2O=7:3) affording (S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-(2-(3-(cyclopropylmethoxy)-4-(methylsulfonamido)-benzoylthio)acetoxy)ethyl)pyridine 1-oxide as a colorless oil (0.032 g, 0.042 mmol, 79% yield, MS/ESI+ 761.26 [MH]+, [αD]=−46.44, c=0.5, MeOH).

Workup

  1. customThe volatiles were removed under vacuum
  2. filtrationthe crude was purified by filtration through a silica gel cartridge (DCM:Et2O=7:3)

Sources & evidence

ORD record
ord-fe5b61fcc78d4d9ebd0d415ddfad73c0
Source dataset
uspto-grants-2016_02
Patent number
US09265768B2

Reaction notes

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