1,2-Dichloroethane → HCID 86681604, compound

HRID 571181Notes

Reaction equation

HRID 571181 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].C(Cl)CCl.[N+:32]([C:35]1[CH:43]=[CH:42][CH:41]=[C:40]2[C:36]=1[C:37](=[O:49])[N:38]([CH2:45][C:46](O)=[O:47])[C:39]2=[O:44])([O-:34])=[O:33]>CN(C=O)C.CN(C1C=CN=CC=1)C>[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:46](=[O:47])[CH2:45][N:38]1[C:37](=[O:49])[C:36]2[C:40](=[CH:41][CH:42]=[CH:43][C:35]=2[N+:32]([O-:34])=[O:33])[C:39]1=[O:44]

Participants

6

Reactant 3

HCID 111,2-DichloroethaneHCID 2727382-(4-nitro-1,3-dioxo-2,3-dihydro-1H-isoindol-2-yl)acetic acidHCID 71092687(S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-hydroxyethyl)pyridine 1-oxide

Product 1

HCID 86681604HCID 86681604, compoundYield 77.3%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6228DimethylformamideSolvent

Procedure

(S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-hydroxyethyl)pyridine 1-oxide (100 mg, 0.238 mmol) was placed in a 50 ml round bottom flask and dissolved in DMF (3 ml); EDC (45.6 mg, 0.238 mmol) was added to it followed by DMAP (29.1 mg, 0.238 mmol) and 2-(4-nitro-1,3-dioxoisoindolin-2-yl)acetic acid (90 mg, 0.357 mmol). The reaction was stirred at RT for 6 hours. The reaction was quenched by adding 30 ml of HCl/H2O (1M) and extracted with EtOAc (30 ml). The organic phase (EtOAc) was extracted with HCl/H2O 1M (30 ml; ×3) and subsequently with K2CO3/H2O (20 ml; ×3). The resulting organic extract was dried over Na2SO4, filtered and the solvent removed under reduced pressure to yield 120 mg of title compound (77% yield). 1H NMR (400 MHz, acetone) δ. ppm 8.35 (d, J=7.50 Hz, 1H), 8.24-8.30 (m, 1H), 8.16-8.24 (m, 3H), 7.16-7.25 (m, 2H), 7.05 (dd, J=8.16, 1.98 Hz, 1H), 6.94 (t, 1H, CHF2), 6.14 (dd, J=9.48, 4.63 Hz, 1H), 4.52 (s, 2H), 4.01 (dd, J=6.62, 3.97 Hz, 2H), 3.54 (dd, J=14.33, 9.48 Hz, 1H), 3.26-3.40 (m, 1H), 1.25-1.38 (m, 1H), 0.56-0.73 (m, 2H), 0.36-0.48 (m, 2H); MS/ESI+ 652.1 [MH]+

Workup

  1. customThe reaction was quenched
  2. additionby adding 30 ml of HCl/H2O (1M)
  3. extractionextracted with EtOAc (30 ml)
  4. extractionThe organic phase (EtOAc) was extracted with HCl/H2O 1M (30 ml; ×3) and subsequently with K2CO3/H2O (20 ml; ×3)
  5. extractionThe resulting organic extract
  6. dry with materialwas dried over Na2SO4
  7. filtrationfiltered
  8. customthe solvent removed under reduced pressure

Sources & evidence

ORD record
ord-3066a559f6f64a11888101193e5f795c
Source dataset
uspto-grants-2015_05
Patent number
US09024027B2

Reaction notes

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