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

HRID 1776557Notes

Reaction equation

HRID 1776557 reaction equation
C(OC([N:8]([C:13]1[CH:14]=[C:15]([CH2:24][C:25]([O:27][CH2:28][C:29]([O:31][C@H:32]([C:43]2[CH:48]=[CH:47][C:46]([O:49][CH:50]([F:52])[F:51])=[C:45]([O:53][CH2:54][CH:55]3[CH2:57][CH2:56]3)[CH:44]=2)[CH2:33][C:34]2[C:39]([Cl:40])=[CH:38][N+:37]([O-:41])=[CH:36][C:35]=2[Cl:42])=[O:30])=[O:26])[CH:16]=[CH:17][C:18]=1[O:19][CH2:20][CH:21]1[CH2:23][CH2:22]1)[S:9]([CH3:12])(=[O:11])=[O:10])=O)(C)(C)C.O1CCOCC1>C(Cl)Cl.Cl>[Cl:42][C:35]1[CH:36]=[N+:37]([O-:41])[CH:38]=[C:39]([Cl:40])[C:34]=1[CH2:33][C@H:32]([O:31][C:29](=[O:30])[CH2:28][O:27][C:25](=[O:26])[CH2:24][C:15]1[CH:16]=[CH:17][C:18]([O:19][CH2:20][CH:21]2[CH2:22][CH2:23]2)=[C:13]([NH:8][S:9]([CH3:12])(=[O:10])=[O:11])[CH:14]=1)[C:43]1[CH:48]=[CH:47][C:46]([O:49][CH:50]([F:52])[F:51])=[C:45]([O:53][CH2:54][CH:55]2[CH2:56][CH2:57]2)[CH:44]=1

Participants

5

Reactant 2

HCID 312751,4-DioxaneHCID 86679514(S)-4-(2-(2-(2-(3-(N-(tert-butoxycarbonyl)-methylsulfonamido)-4-(cyclopropylmethoxy)phenyl)acetoxy)acetoxy)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)ethyl)-3,5-dichloropyridine 1-oxide

Product 1

HCID 86679513(S)-3,5-dichloro-4-(2-(2-(2-(4-(cyclopropylmethoxy)-3-(methylsulfonamido)phenyl)acetoxy)acetoxy)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)ethyl)pyridine 1-oxideYield 26.9%

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of crude (S)-4-(2-(2-(2-(3-(N-(tert-butoxycarbonyl)-methylsulfonamido)-4-(cyclopropylmethoxy)phenyl)acetoxy)acetoxy)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)ethyl)-3,5-dichloropyridine 1-oxide (theoric 0.501 mmol) in DCM (5 ml), HCl 4M in dioxane (1.309 ml, 5.23 mmol) was added and the mixture was reacted for 4 hours at RT. The solvents were evaporated to dryness, and the resulting crude was purified by preparative LC-MS recovering the desired product (102.5 mg, 0.135 mmol, 26.9% yield over two steps, MS/ESI+ 759.46 [MH]+, [αD]=+47.84, c=0.25, DCM).

Workup

  1. customthe mixture was reacted for 4 hours at RT
  2. customThe solvents were evaporated to dryness
  3. customthe resulting crude was purified by preparative LC-MS

Sources & evidence

ORD record
ord-2d9d0be2197d442a9ad79cc843c1bc65
Source dataset
uspto-grants-2016_02
Patent number
US09265768B2

Reaction notes

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