Potassium Carbonate → 7-[2-(4-Cyano-2-fluoro-phenoxy)-ethyl]-9-oxa-3,7-diaza-bicyclo[3.3.1]nonane-3-carboxylic acid tert-butyl ester

HRID 1992366ノート

反応式

HRID 1992366 の反応式
Br[CH2:2][CH2:3][O:4][C:5]1[CH:12]=[CH:11][C:8]([C:9]#[N:10])=[CH:7][C:6]=1[F:13].[C:14]([O:18][C:19]([N:21]1[CH2:28][CH:27]2[O:29][CH:23]([CH2:24][NH:25][CH2:26]2)[CH2:22]1)=[O:20])([CH3:17])([CH3:16])[CH3:15].C([O-])([O-])=O.[K+].[K+]>C(#N)C>[C:14]([O:18][C:19]([N:21]1[CH2:22][CH:23]2[O:29][CH:27]([CH2:26][N:25]([CH2:2][CH2:3][O:4][C:5]3[CH:12]=[CH:11][C:8]([C:9]#[N:10])=[CH:7][C:6]=3[F:13])[CH2:24]2)[CH2:28]1)=[O:20])([CH3:17])([CH3:15])[CH3:16]

参加物

5

反応物 3

HCID 11430Potassium CarbonateHCID 159788884-(2-Bromoethoxy)-3-fluorobenzonitrileHCID 185404123-Boc-9-oxa-3,7-diazabicyclo[3.3.1]nonane

生成物 1

HCID 685190747-[2-(4-Cyano-2-fluoro-phenoxy)-ethyl]-9-oxa-3,7-diaza-bicyclo[3.3.1]nonane-3-carboxylic acid tert-butyl ester収率 65.8%

試薬・触媒・溶媒 1

HCID 6342Acetonitrile溶媒

反応条件

温度
60 °C

実験手順

A suspension of 4-(2-Bromo-ethoxy)-3-fluoro-benzonitrile (21.6 g, 0.0885 mol, from step (v) above), 9-oxa-3,7-diaza-bicyclo[3.3.1]nonane-3-carboxylic acid tert-butyl ester (21.1 g, 0.07965 mol; see WO 01/28992) and dry K2CO3 (48.9 g, 0.354 mol) in 200 ml of dry acetonitrile was stirred at 60° C. for five days under N2 atmosphere. The reaction mixture was filtered through celite and filtrate was concentrated under reduced pressure. The residue was purified by column chromatography over silica gel using 27% ethyl acetate in petroleum ether, as eluent to yield the sub-title compound (20.5 g) as a solid.

後処理

  1. filtrationThe reaction mixture was filtered through celite and filtrate
  2. concentrationwas concentrated under reduced pressure
  3. customThe residue was purified by column chromatography over silica gel using 27% ethyl acetate in petroleum ether, as eluent

出典と根拠

ORDレコード
ord-e4becfefd4f944aeb1fc3ee09fcd2a88
出典データセット
uspto-grants-2010_01
特許番号
US07648985B2

反応ノート

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