1,2-Dichloroethane → HCID 86681611, compound

HRID 571188Notes

Reaction equation

HRID 571188 reaction equation
[CH2:1]([O:8][C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][CH:17]=1)[N:14]([CH2:18][C:19]([OH:21])=[O:20])[CH:13]=[CH:12]2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Cl:22][C:23]1[CH:24]=[N+:25]([O-:48])[CH:26]=[C:27]([Cl:47])[C:28]=1[CH2:29][C@@H:30]([C:32]1[CH:37]=[CH:36][C:35]([O:38][CH:39]([F:41])[F:40])=[C:34]([O:42][CH2:43][CH:44]2[CH2:46][CH2:45]2)[CH:33]=1)O.C(Cl)CCl>C(Cl)Cl.CN(C1C=CN=CC=1)C>[CH2:1]([O:8][C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][CH:17]=1)[N:14]([CH2:18][C:19]([O:21][C@H:30]([C:32]1[CH:37]=[CH:36][C:35]([O:38][CH:39]([F:40])[F:41])=[C:34]([O:42][CH2:43][CH:44]3[CH2:45][CH2:46]3)[CH:33]=1)[CH2:29][C:28]1[C:27]([Cl:47])=[CH:26][N+:25]([O-:48])=[CH:24][C:23]=1[Cl:22])=[O:20])[CH:13]=[CH:12]2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 3

HCID 111,2-DichloroethaneHCID 21906919HCID 21906919, compoundHCID 71092687HCID 71092687, compound

Product 1

HCID 86681611HCID 86681611, compoundYield 80.1%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

To a mixture of 2-(5-(benzyloxy)-1H-indol-1-yl)acetic acid (164 mg, 0.583 mmol) in DCM (20 ml), (S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-hydroxyethyl)pyridine 1-oxide (245 mg, 0.583 mmol), EDC (335 mg, 1.749 mmol) and DMAP (35.6 mg, 0.291 mmol) were added, and the reaction was stirred at room temperature for 5 hours. The organic solution was washed with NaHCO3 sat. sol. and 1N HCl, dried over Na2SO4, filtered and evaporated. The crude was purified by flash chromatography on silica gel (DCM/MeOH from 99.5:0.5 to 98.5:1.5) affording (S)-4-(2-(2-(5-(benzyloxy)-1H-indol-1-yl)acetoxy)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)ethyl)-3,5-dichloropyridine 1-oxide (319 mg, 0.467 mmol, 80% yield). MS/ESI+ 683.0 [MH]+.

Workup

  1. additionwere added
  2. washThe organic solution was washed with NaHCO3 sat. sol. and 1N HCl
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. customevaporated
  6. customThe crude was purified by flash chromatography on silica gel (DCM/MeOH from 99.5:0.5 to 98.5:1.5)

Sources & evidence

ORD record
ord-365de196f8dd44ada0ff4d4c243f1790
Source dataset
uspto-grants-2015_05
Patent number
US09024027B2

Reaction notes

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