1,2-Dichloroethane → HCID 86679476, compound

HRID 1776520Notes

Reaction equation

HRID 1776520 reaction equation
[C:1]([O:20][CH2:21][CH2:22][C:23]([OH:25])=[O:24])([C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(Cl)CCl.[Cl:30][C:31]1[CH:32]=[N+:33]([O-:56])[CH:34]=[C:35]([Cl:55])[C:36]=1[CH2:37][C@@H:38]([C:40]1[CH:45]=[CH:44][C:43]([O:46][CH:47]([F:49])[F:48])=[C:42]([O:50][CH2:51][CH:52]2[CH2:54][CH2:53]2)[CH:41]=1)O>C(Cl)Cl.CN(C1C=CN=CC=1)C>[Cl:30][C:31]1[CH:32]=[N+:33]([O-:56])[CH:34]=[C:35]([Cl:55])[C:36]=1[CH2:37][C@@H:38]([C:40]1[CH:45]=[CH:44][C:43]([O:46][CH:47]([F:49])[F:48])=[C:42]([O:50][CH2:51][CH:52]2[CH2:54][CH2:53]2)[CH:41]=1)[O:24][C:23](=[O:25])[CH2:22][CH2:21][O:20][C:1]([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)([C:14]1[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 3

HCID 111,2-DichloroethaneHCID 18992122HCID 18992122, compoundHCID 71092687(S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-hydroxyethyl)pyridine 1-oxide

Product 1

HCID 86679476HCID 86679476, compoundYield 54.3%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

To a mixture of 3-(trityloxy)propanoic acid (0.5 g, 1.504 mmol) and EDC (0.865 g, 4.51 mmol) in dry DCM (20 ml), (S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-hydroxyethyl)pyridine 1-oxide (0.632 g, 1.504 mmol) and DMAP (0.184 g, 1.504 mmol) were added, and the resulting solution was stirred at RT overnight. The solvent was evaporated and the residue was partitioned between EtOAc and a sat. sol. of NaHCO3. The organic layer was washed with aqueous 3% citric acid, with brine and dried over Na2SO4. The solvent was removed under vacuum and the residue was purified by flash chromatography on silica gel column (DCM:MeOH: 32% aq. NH4OH=98:2:0.2) affording (S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-(3-(trityloxy)propanoyloxy)ethyl)pyridine 1-oxide (0.6 g, 0.817 mmol, 54.3% yield, MS/ESI+ 756.3 [MNa]+).

Workup

  1. additionwere added
  2. customThe solvent was evaporated
  3. customthe residue was partitioned between EtOAc
  4. washThe organic layer was washed with aqueous 3% citric acid, with brine
  5. dry with materialdried over Na2SO4
  6. customThe solvent was removed under vacuum
  7. customthe residue was purified by flash chromatography on silica gel column (DCM:MeOH: 32% aq. NH4OH=98:2:0.2)

Sources & evidence

ORD record
ord-4f183ee50dd347148370e2f1eae8551a
Source dataset
uspto-grants-2016_02
Patent number
US09265768B2

Reaction notes

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