1,2-Dichloroethane → HCID 86681663, compound

HRID 571249Notes

Reaction equation

HRID 571249 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][C:11]=1[NH:12][S:13]([CH3:16])(=[O:15])=[O:14])[C:8](=[O:17])[N:7]([CH2:18][C:19]([OH:21])=[O:20])[C:6]2=[O:22].[Cl:23][C:24]1[CH:25]=[N+:26]([O-:49])[CH:27]=[C:28]([Cl:48])[C:29]=1[CH2:30][C@@H:31]([C:33]1[CH:38]=[CH:37][C:36]([O:39][CH:40]([F:42])[F:41])=[C:35]([O:43][CH2:44][CH:45]2[CH2:47][CH2:46]2)[CH:34]=1)O.C(Cl)CCl>CN(C1C=CN=CC=1)C.C(Cl)Cl>[Cl:23][C:24]1[CH:25]=[N+:26]([O-:49])[CH:27]=[C:28]([Cl:48])[C:29]=1[CH2:30][C@@H:31]([C:33]1[CH:38]=[CH:37][C:36]([O:39][CH:40]([F:42])[F:41])=[C:35]([O:43][CH2:44][CH:45]2[CH2:47][CH2:46]2)[CH:34]=1)[O:20][C:19](=[O:21])[CH2:18][N:7]1[C:6](=[O:22])[C:5]2[C:9](=[CH:10][C:11]([NH:12][S:13]([CH3:16])(=[O:15])=[O:14])=[C:3]([O:2][CH3:1])[CH:4]=2)[C:8]1=[O:17]

Participants

6

Reactant 3

HCID 111,2-DichloroethaneHCID 71092687HCID 71092687, compoundHCID 86681662HCID 86681662, compound

Product 1

HCID 86681663HCID 86681663, compoundYield 24%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent2×

Procedure

A mixture of 2-(5-methoxy-6-(methylsulfonamido)-1,3-dioxoisoindolin-2-yl)acetic acid (0.183 g, 0.557 mmol), (S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-hydroxyethyl)pyridine 1-oxide (0.234 g, 0.557 mmol), EDC (0.321 g, 1.672 mmol) and DMAP (0.034 g, 0.279 mmol) in DCM (20 ml) was stirred at room temperature for 2 hours. The mixture was diluted with DCM and washed with 1N HCl, 5% NaHCO3 and brine. The organic phase was dried over sodium sulfate, the solvent was removed, and the crude was purified by flash chromatography on silica gel cartridge (DCM:ethyl acetate from 1:1 to 4:1) affording (S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-(2-(5-methoxy-6-(methylsulfonamido)-1,3-dioxoisoindolin-2-yl)acetoxy)ethyl)pyridine 1-oxide as a pale orange solid (0.097 g, 0.133 mmol, 24% yield). MS/ESI+ 730.13 [MH]+; [αD]=−33.40, c=0.43, DCM; 1H NMR (300 MHz, DMSO-d6) δ ppm 9.54 (br. s., 1H), 8.44 (s, 2H), 7.77 (s, 1H), 7.55 (s, 1H), 7.19 (d, 1H), 7.08 (d, 1H), 6.96 (dd, 1H), 7.08 (t, 1H), 6.01 (dd, 1H), 4.39 (s, 2H), 4.04 (s, 3H), 3.93 (d, 2H), 3.39 (dd, 1H), 3.23 (dd, 1H), 3.15 (s, 3H), 1.01-1.37 (m, 1H), 0.50-0.72 (m, 2H), 0.25-0.45 (m, 2H)

Workup

  1. washwashed with 1N HCl, 5% NaHCO3 and brine
  2. dry with materialThe organic phase was dried over sodium sulfate
  3. customthe solvent was removed
  4. customthe crude was purified by flash chromatography on silica gel cartridge (DCM:ethyl acetate from 1:1 to 4:1)

Sources & evidence

ORD record
ord-34ec532f8ae24aac8c71c43654d4a8e0
Source dataset
uspto-grants-2015_05
Patent number
US09024027B2

Reaction notes

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