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

HRID 1776517Notes

Reaction equation

HRID 1776517 reaction equation
C(OC([N:8]([C:13]1[CH:51]=[CH:50][C:16]([C:17]([O: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][O: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-DioxaneHCID 89459927(S)-4-(2-(2-(4-(N-(tert-butoxycarbonyl)methyl-sulfonamido)-3-(cyclopropylmethoxy)benzoyloxy)acetoxy)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)ethyl)-3,5-dichloropyridine 1-oxide

Product 1

HCID 86679474(S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-(2-(3-(cyclopropylmethoxy)-4-(methylsulfonamido)-benzoyloxy)acetoxy)ethyl)pyridine 1-oxideYield 81%

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of (S)-4-(2-(2-(4-(N-(tert-butoxycarbonyl)methylsulfonamido)-3-(cyclopropylmethoxy)benzoyloxy)acetoxy)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)ethyl)-3,5-dichloropyridine 1-oxide (2.457 g, 2.91 mmol) in dry DCM (85 ml), HCl 4M in dioxane (7.26 ml, 29.1 mmol) was added, and the reaction was stirred at RT overnight. Then the solvent was evaporated and the residue was purified by flash chromatography on silica gel (eluent: DCM/MeOH 99:1). Combined fractions were evaporated and the resulting solid was triturated with EtOH/MeOH 95:5 to afford (S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-(2-(3-(cyclopropylmethoxy)-4-(methylsulfonamido)-benzoyloxy)acetoxy)ethyl)pyridine 1-oxide as a white solid (1.761 g, 2.362 mmol, 81% yield, MS/ESI+ 745.13 [MH]+, [αD]=−34.69, c=0.49, DCM).

Workup

  1. customThen the solvent was evaporated
  2. customthe residue was purified by flash chromatography on silica gel (eluent: DCM/MeOH 99:1)
  3. customCombined fractions were evaporated
  4. customthe resulting solid was triturated with EtOH/MeOH 95:5

Sources & evidence

ORD record
ord-d04e0ca254b54270a7ad5b60c7d94bd9
Source dataset
uspto-grants-2016_02
Patent number
US09265768B2

Reaction notes

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