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

HRID 1776554ノート

反応式

HRID 1776554 の反応式
[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

参加物

7

反応物 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

生成物 1

HCID 86679511(S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-(2-(trityloxy)acetoxy)ethyl)pyridine 1-oxide収率 62.8%

試薬・触媒・溶媒 2

HCID 142844-(Dimethylamino)pyridine触媒HCID 6344Dichloromethane溶媒

実験手順

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]+).

後処理

  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)

出典と根拠

ORDレコード
ord-3ca39d08716443cabb4be178f3b1a2b9
出典データセット
uspto-grants-2016_02
特許番号
US09265768B2

反応ノート

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