1,2-Dichloroethane → HCID 86681607, compound

HRID 571183Notes

Reaction equation

HRID 571183 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]1([CH2:37][C:38](O)=[O:39])[C:36]2[C:31](=[CH:32][CH:33]=[CH:34][CH:35]=2)[CH:30]=[CH:29]1.C(Cl)CCl>CN(C1C=CN=CC=1)C.C(Cl)Cl>[N:28]1([CH2:37][C:38]([O:10][C@H:9]([C:11]2[CH:16]=[CH:15][C:14]([O:17][CH:18]([F:20])[F:19])=[C:13]([O:21][CH2:22][CH:23]3[CH2:25][CH2:24]3)[CH:12]=2)[CH2:8][C:7]2[C:6]([Cl:26])=[CH:5][N+:4]([O-:27])=[CH:3][C:2]=2[Cl:1])=[O:39])[C:36]2[C:31](=[CH:32][CH:33]=[CH:34][CH:35]=2)[CH:30]=[CH:29]1

Participants

6

Reactant 3

HCID 111,2-DichloroethaneHCID 904481H-Indole-1-acetic acidHCID 71092687(S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-hydroxyethyl)pyridine 1-oxide

Product 1

HCID 86681607HCID 86681607, compoundYield 72.8%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

A mixture of (S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-hydroxyethyl)pyridine 1-oxide (0.615 g, 1.463 mmol), 2-(1H-indol-1-yl)acetic acid (0.282 g, 1.610 mmol), EDC (0.842 g, 4.39 mmol), and DMAP (0.268 g, 2.195 mmol) in DCM (20 ml) was stirred at room temperature overnight. The reaction was washed with 1N HCl, aqueous NaHCO3 and brine; the organic phase was dried over Na2SO4 and evaporated to dryness. The crude was purified by flash chromatography on silica gel column (DCM/MeOH from 99/1 to 98/2) to afford (S)-4-(2-(2-(1H-indol-1-yl)acetoxy)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)ethyl)-3,5-dichloropyridine 1-oxide (0.615 g, 1.065 mmol, 72.8% yield). MS/ESI+ 577.2 [MH]+; [αD]=+5.500, c=0.44, DCM; 1H NMR (300 MHz, DMSO-d6) d ppm 8.52 (s, 2H), 7.48-7.63 (m, 1H), 7.27 (d, 1H), 7.13-7.19 (m, 2H), 7.10 (td, 1H), 7.00-7.05 (m, 1H), 6.99 (d, 1H), 6.92 (dd, 1H), 7.06 (t, 1H), 6.45 (dd, 1H), 6.02 (dd, 1H), 5.23 (d, 1H), 5.05 (d, 1H), 3.84 (d, 2H), 3.42 (dd, 1H), 3.20 (dd, 1H), 1.13-1.34 (m, 1H), 0.49-0.67 (m, 2H), 0.29-0.46 (m, 2H).

Workup

  1. washThe reaction was washed with 1N HCl, aqueous NaHCO3 and brine
  2. dry with materialthe organic phase was dried over Na2SO4
  3. customevaporated to dryness
  4. customThe crude was purified by flash chromatography on silica gel column (DCM/MeOH from 99/1 to 98/2)

Sources & evidence

ORD record
ord-9ff6fd39e9f7452b9208912d71015a49
Source dataset
uspto-grants-2015_05
Patent number
US09024027B2

Reaction notes

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