1,2-Dichloroethane → (S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-(1-(4-nitrophenylsulfonyl)-1H-pyrrole-2-carbonyloxy)-ethyl)pyridine 1-oxide

HRID 59728Notes

Reaction equation

HRID 59728 reaction equation
[Cl:1][C:2]1[CH:3]=[N+:4]([O-:27])[CH:5]=[C:6]([Cl:26])[C:7]=1[CH2:8][C@@H:9]([C:11]1[CH:16]=[CH:15][C:14]([O:17][CH:18]([F:20])[F:19])=[C:13]([O:21][CH2:22][CH:23]2[CH2:25][CH2:24]2)[CH:12]=1)[OH:10].[N+:28]([C:31]1[CH:36]=[CH:35][C:34]([S:37]([N:40]2[CH:44]=[CH:43][CH:42]=[C:41]2[C:45](O)=[O:46])(=[O:39])=[O:38])=[CH:33][CH:32]=1)([O-:30])=[O:29].C(Cl)CCl>CN(C1C=CN=CC=1)C.C(Cl)Cl>[Cl:1][C:2]1[CH:3]=[N+:4]([O-:27])[CH:5]=[C:6]([Cl:26])[C:7]=1[CH2:8][C@@H:9]([C:11]1[CH:16]=[CH:15][C:14]([O:17][CH:18]([F:20])[F:19])=[C:13]([O:21][CH2:22][CH:23]2[CH2:25][CH2:24]2)[CH:12]=1)[O:10][C:45]([C:41]1[N:40]([S:37]([C:34]2[CH:35]=[CH:36][C:31]([N+:28]([O-:30])=[O:29])=[CH:32][CH:33]=2)(=[O:38])=[O:39])[CH:44]=[CH:43][CH:42]=1)=[O:46]

Participants

6

Reactant 3

HCID 111,2-DichloroethaneHCID 71092687(S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-hydroxyethyl)pyridine 1-oxideHCID 867038341-(4-nitrophenylsulfonyl)-1H-pyrrole-2-carboxylic acid

Product 1

HCID 86703836(S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-(1-(4-nitrophenylsulfonyl)-1H-pyrrole-2-carbonyloxy)-ethyl)pyridine 1-oxideYield 27.8%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent2×

Procedure

A mixture of (S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-hydroxyethyl)pyridine 1-oxide (206 mg, 0.490 mmol), 1-(4-nitrophenylsulfonyl)-1H-pyrrole-2-carboxylic acid (Int. 5) (160 mg, 0.539 mmol), EDC (282 mg, 1.471 mmol) and DMAP (59.9 mg, 0.490 mmol) in DCM (10 ml) was stirred at RT for 24 hours. The reaction was diluted with DCM and washed with 1N HCl, sat. NaHCO3 (40 ml), and finally with brine. The organic phase was dried over sodium sulfate and the solvent was removed under vacuum; the crude was purified by preparative HPLC-Method 1 to yield (S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-(1-(4-nitrophenylsulfonyl)-1H-pyrrole-2-carbonyloxy)ethyl)pyridine 1-oxide (Int. 6) (95 mg, 0.136 mmol, MS/ESI+698.05 [MH]+, [αD]=−40.97, c=0.6, DCM).

Workup

  1. washwashed with 1N HCl, sat. NaHCO3 (40 ml)
  2. dry with materialThe organic phase was dried over sodium sulfate
  3. customthe solvent was removed under vacuum
  4. customthe crude was purified by preparative HPLC-Method 1

Sources & evidence

ORD record
ord-ff499b35fd0249fda2f80b8631f1b99f
Source dataset
uspto-grants-2016_09
Patent number
US09440954B2

Reaction notes

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