1,2-Dichloroethane → (S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-(2-(trityloxy)acetoxy)ethyl)pyridine 1-oxide

HRID 1776554Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1776554
[C:1]([O:20][CH2:21][C:22]([OH:24])=[O:23])([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.[Cl:25][C:26]1[CH:27]=[N+:28]([O-:51])[CH:29]=[C:30]([Cl:50])[C:31]=1[CH2:32][C@@H:33]([C:35]1[CH:40]=[CH:39][C:38]([O:41][CH:42]([F:44])[F:43])=[C:37]([O:45][CH2:46][CH:47]2[CH2:49][CH2:48]2)[CH:36]=1)O.C(Cl)CCl.C([O-])([O-])=O.[K+].[K+]>C(Cl)Cl.CN(C1C=CN=CC=1)C>[Cl:25][C:26]1[CH:27]=[N+:28]([O-:51])[CH:29]=[C:30]([Cl:50])[C:31]=1[CH2:32][C@@H:33]([C:35]1[CH:40]=[CH:39][C:38]([O:41][CH:42]([F:44])[F:43])=[C:37]([O:45][CH2:46][CH:47]2[CH2:49][CH2:48]2)[CH:36]=1)[O:23][C:22](=[O:24])[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

Komponenten

7

Edukt 4

HCID 111,2-DichloroethaneHCID 11430Potassium CarbonateHCID 122307892-(Trityloxy)acetic acidHCID 71092687(S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-hydroxyethyl)pyridine 1-oxide

Produkt 1

HCID 86679511(S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-(2-(trityloxy)acetoxy)ethyl)pyridine 1-oxideAusbeute 62,8 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 142844-(Dimethylamino)pyridineKatalysatorHCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

To a solution of 2-(trityloxy)acetic acid (7.2 g, 22.62 mmol) in DCM (250 ml), (S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-hydroxyethyl)pyridine 1-oxide (7.92 g, 18.85 mmol), EDC (4.34 g, 22.62 mmol), and DMAP (4.60 g, 37.7 mmol) were added at RT. The solution was stirred at the same temperature overnight. A sat. sol. of K2CO3 was added, and the organic phase was separated, washed with HCl 2N and brine, dried over Na2SO4 and evaporated under vacuum. The resulting brown crude was purified by flash chromatography on silica gel (DCM 100% as eluent). (S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-(2-(trityloxy)acetoxy)ethyl)pyridine 1-oxide was obtained (8.53 g, 11.84 mmol, 62.8% yield, MS/ESI+ 720.1 [MH]+).

Aufarbeitung

  1. customthe organic phase was separated
  2. washwashed with HCl 2N and brine
  3. dry with materialdried over Na2SO4
  4. customevaporated under vacuum
  5. customThe resulting brown crude was purified by flash chromatography on silica gel (DCM 100% as eluent)

Quellen und Nachweise

ORD-Eintrag
ord-3ca39d08716443cabb4be178f3b1a2b9
Quelldatensatz
uspto-grants-2016_02
Patentnummer
US09265768B2

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