1,4-Dioxane → HCID 71542651, compound

HRID 1776649Notes

Reaction equation

HRID 1776649 reaction equation
C(OC([N:8]([C:13]1[CH:53]=[CH:52][C:16]([C:17]([O:19][C:20]([CH3:51])([CH3:50])[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:54][CH2:55][CH:56]1[CH2:58][CH2:57]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[CH2:48][CH2:49]2)[CH:36]=1)[O:23][C:21](=[O:22])[C:20]([O:19][C:17](=[O:18])[C:16]1[CH:52]=[CH:53][C:13]([NH:8][S:9]([CH3:12])(=[O:11])=[O:10])=[C:14]([O:54][CH2:55][CH:56]2[CH2:58][CH2:57]2)[CH:15]=1)([CH3:50])[CH3:51]

Participants

5

Reactant 2

HCID 312751,4-Dioxane2×HCID 89455315HCID 89455315, compound

Product 1

HCID 71542651HCID 71542651, compoundYield 33.6%

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)benzoyloxy)-2-methylpropanoyloxy)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)ethyl)-3,5-dichloropyridine 1-oxide (168 mg, 0.192 mmol) in dry DCM (2 ml), HCl 4M in dioxane (144 μl, 0.577 mmol) was added with stirring at RT for 2 days. Additional HCl 4M in dioxane (144 μl, 0.577 mmol) was freshly added and the stirring was continued for further 3 days. The volatiles were removed under vacuum, and the crude was purified by preparative HPLC. After evaporation of the solvent, the residue was triturated with iPr2O and collected by filtration to give (S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-(2-(3-(cyclopropylmethoxy)-4-(methylsulfonamido)benzoyloxy)-2-methylpropanoyloxy)ethyl)pyridine 1-oxide as a white solid (50 mg, 0.065 mmol, 33.6% yield, MS/ESI+ 773.29 [MH]+, [αD]=−18.13, c=0.60, MeOH).

Workup

  1. waitthe stirring was continued for further 3 days
  2. customThe volatiles were removed under vacuum
  3. customthe crude was purified by preparative HPLC
  4. customAfter evaporation of the solvent
  5. customthe residue was triturated with iPr2O
  6. filtrationcollected by filtration

Sources & evidence

ORD record
ord-5521d81a056d430c824dd0cd700f33a5
Source dataset
uspto-grants-2016_02
Patent number
US09265768B2

Reaction notes

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