1,2-Dichloroethane → (S)-3,5-dichloro-4-(2-(2-(6-chloronicotinoyloxy)acetoxy)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)ethyl)pyridine 1-oxide

HRID 1776650Notes

Reaction equation

HRID 1776650 reaction equation
[Cl:1][C:2]1[CH:3]=[N+:4]([O-:31])[CH:5]=[C:6]([Cl:30])[C:7]=1[CH2:8][C@@H:9]([C:15]1[CH:20]=[CH:19][C:18]([O:21][CH:22]([F:24])[F:23])=[C:17]([O:25][CH2:26][CH:27]2[CH2:29][CH2:28]2)[CH:16]=1)[O:10][C:11](=[O:14])[CH2:12][OH:13].[Cl:32][C:33]1[CH:41]=[CH:40][C:36]([C:37](O)=[O:38])=[CH:35][N:34]=1.C(Cl)CCl>C(Cl)Cl.CN(C1C=CN=CC=1)C>[Cl:30][C:6]1[CH:5]=[N+:4]([O-:31])[CH:3]=[C:2]([Cl:1])[C:7]=1[CH2:8][C@H:9]([O:10][C:11](=[O:14])[CH2:12][O:13][C:37](=[O:38])[C:36]1[CH:40]=[CH:41][C:33]([Cl:32])=[N:34][CH:35]=1)[C:15]1[CH:20]=[CH:19][C:18]([O:21][CH:22]([F:24])[F:23])=[C:17]([O:25][CH2:26][CH:27]2[CH2:29][CH2:28]2)[CH:16]=1

Participants

6

Reactant 3

HCID 111,2-DichloroethaneHCID 792226-Chloronicotinic acidHCID 86679512(S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-(2-hydroxyacetoxy)ethyl)pyridine 1-oxide

Product 1

HCID 86679594(S)-3,5-dichloro-4-(2-(2-(6-chloronicotinoyloxy)acetoxy)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)ethyl)pyridine 1-oxideYield 78%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

To a mixture of (S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-(2-hydroxyacetoxy)ethyl)pyridine 1-oxide (See Scheme 21, step 6-9) (200 mg, 0.418 mmol), 6-chloronicotinic acid (72.5 mg, 0.460 mmol) and EDC (240 mg, 1.255 mmol) in dry DCM (10 ml), DMAP (51.1 mg, 0.418 mmol) was added, and stirring was continued for a week-end at room temperature. The solvent was evaporated; the residue was portioned between sat. sol. NaHCO3 and ethyl acetate, the organic phase was washed with brine, dried over sodium sulfate and evaporated, the residue was purified by flash chromatography on silica gel (eluent: DCM/MeOH/32% NH4OH 98/2/0.2) and (S)-3,5-dichloro-4-(2-(2-(6-chloronicotinoyloxy)acetoxy)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)ethyl)pyridine 1-oxide was obtained as a white solid (202 mg, 0.327 mmol, 78% yield, MS/ESI+ 617.2 [MH]+).

Workup

  1. additionwas added
  2. waitwas continued for a week
  3. customat room temperature
  4. customThe solvent was evaporated
  5. washthe organic phase was washed with brine
  6. dry with materialdried over sodium sulfate
  7. customevaporated
  8. customthe residue was purified by flash chromatography on silica gel (eluent: DCM/MeOH/32% NH4OH 98/2/0.2)

Sources & evidence

ORD record
ord-1e787623bf4447cc8b7c1621cd3a086f
Source dataset
uspto-grants-2016_02
Patent number
US09265768B2

Reaction notes

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