1,4-Dioxane → (S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-(3-(3-(cyclopropylmethoxy)-4-(methylsulfonamido)benzoyloxy)propanoyloxy)ethyl)-pyridine 1-oxide

HRID 1776523Notes

Reaction equation

HRID 1776523 reaction equation
C(OC([N:8]([C:13]1[CH:52]=[CH:51][C:16]([C:17]([O:19][CH2:20][CH2:21][C:22]([O:24][C@H:25]([C:36]2[CH:41]=[CH:40][C:39]([O:42][CH:43]([F:45])[F:44])=[C:38]([O:46][CH2:47][CH:48]3[CH2:50][CH2:49]3)[CH:37]=2)[CH2:26][C:27]2[C:32]([Cl:33])=[CH:31][N+:30]([O-:34])=[CH:29][C:28]=2[Cl:35])=[O:23])=[O:18])=[CH:15][C:14]=1[O:53][CH2:54][CH:55]1[CH2:57][CH2:56]1)[S:9]([CH3:12])(=[O:11])=[O:10])=O)(C)(C)C.O1CCOCC1>C(Cl)Cl.Cl>[Cl:35][C:28]1[CH:29]=[N+:30]([O-:34])[CH:31]=[C:32]([Cl:33])[C:27]=1[CH2:26][C@@H:25]([C:36]1[CH:41]=[CH:40][C:39]([O:42][CH:43]([F:44])[F:45])=[C:38]([O:46][CH2:47][CH:48]2[CH2:50][CH2:49]2)[CH:37]=1)[O:24][C:22](=[O:23])[CH2:21][CH2:20][O:19][C:17](=[O:18])[C:16]1[CH:51]=[CH:52][C:13]([NH:8][S:9]([CH3:12])(=[O:11])=[O:10])=[C:14]([O:53][CH2:54][CH:55]2[CH2:56][CH2:57]2)[CH:15]=1

Participants

5

Reactant 2

HCID 312751,4-DioxaneHCID 89455835(S)-4-(2-(3-(4-(N-(tert-butoxycarbonyl)methylsulfonamido)-3-(cyclopropylmethoxy)benzoyloxy)propanoyloxy)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)ethyl)-3,5-dichloropyridine 1-oxide

Product 1

HCID 86679478(S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-(3-(3-(cyclopropylmethoxy)-4-(methylsulfonamido)benzoyloxy)propanoyloxy)ethyl)-pyridine 1-oxideYield 86%

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of (S)-4-(2-(3-(4-(N-(tert-butoxycarbonyl)methylsulfonamido)-3-(cyclopropylmethoxy)benzoyloxy)propanoyloxy)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)ethyl)-3,5-dichloropyridine 1-oxide (0.450 g, 0.523 mmol) in dry DCM (15 ml), 4M HCl in dioxane (0.654 ml, 2.62 mmol) was added. The resulting mixture was stirred at RT for 4 days. The solvent was evaporated and the residue was purified by trituration with Et2O (30 ml) affording (S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-(3-(3-(cyclopropylmethoxy)-4-(methylsulfonamido)benzoyloxy)propanoyloxy)ethyl)-pyridine 1-oxide (0.340 g, 0.448 mmol, 86% yield, MS/ESI+759.31 [MH]+, [αD]=−8.9, c=0.6, DCM).

Workup

  1. customThe solvent was evaporated
  2. customthe residue was purified by trituration with Et2O (30 ml)

Sources & evidence

ORD record
ord-36fcc8401bc34e3fb74cdc7b8302eaef
Source dataset
uspto-grants-2016_02
Patent number
US09265768B2

Reaction notes

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