Sodium Hydroxide → 4-{(2R)-2-[({(2S)-2-hydroxy-3-[4-(2-methoxyethyl)phenoxy]propyl}amino)methyl]-3,4-dihydro-2H-chromen-6-yl}benzoic Acid

HRID 47688ノート

反応式

HRID 47688 の反応式
[CH3:1][O:2][CH2:3][CH2:4][C:5]1[CH:15]=[CH:14][C:8]([O:9][CH2:10][C@@H:11]2[CH2:13][O:12]2)=[CH:7][CH:6]=1.[NH2:16][CH2:17][C@H:18]1[CH2:27][CH2:26][C:25]2[C:20](=[CH:21][CH:22]=[C:23]([C:28]3[CH:37]=[CH:36][C:31]([C:32]([O:34]C)=[O:33])=[CH:30][CH:29]=3)[CH:24]=2)[O:19]1.[OH-].[Na+]>O1CCOCC1>[OH:12][C@H:11]([CH2:10][O:9][C:8]1[CH:14]=[CH:15][C:5]([CH2:4][CH2:3][O:2][CH3:1])=[CH:6][CH:7]=1)[CH2:13][NH:16][CH2:17][C@H:18]1[CH2:27][CH2:26][C:25]2[C:20](=[CH:21][CH:22]=[C:23]([C:28]3[CH:29]=[CH:30][C:31]([C:32]([OH:34])=[O:33])=[CH:36][CH:37]=3)[CH:24]=2)[O:19]1

参加物

5

反応物 3

HCID 14798Sodium HydroxideHCID 9902206methyl 4-[(2R)-2-(aminomethyl)-3,4-dihydro-2H-chromen-6-yl]benzoateHCID 10976684(S)-3-[4-(2-Methoxyethyl)phenoxy]-1,2-epoxypropane

生成物 1

HCID 98702424-{(2R)-2-[({(2S)-2-hydroxy-3-[4-(2-methoxyethyl)phenoxy]propyl}amino)methyl]-3,4-dihydro-2H-chromen-6-yl}benzoic Acid収率 10.5%

試薬・触媒・溶媒 1

HCID 312751,4-Dioxane溶媒

反応条件

温度
80 °C

実験手順

To a solution of epoxide (Example 16, 0.25 mmol) in 2 mL of aqueous 1,4-dioxane (10% water) was added methyl 4-[(2R)-2-(aminomethyl)-3,4-dihydro-2H-chromen-6-yl]benzoate (40 mg, 0.13 mmol). The mixture was stirred at 80° C. for 72 hours and allowed to cool to room temperature. When ambient temperature was achieved, 1N aqueous sodium hydroxide (1 mL) was added to the solution at room temperature, and stirring continued for another 0.5 hour. The product was then purified by preparative HPLC (Gradient 0-70% Acetonitrile/0.1% aq. TFA) to obtain 6.7 mg of product (as a TFA salt). MH+492.4 (free base).

後処理

  1. temperatureto cool to room temperature
  2. customWhen ambient temperature
  3. stirringstirring
  4. waitcontinued for another 0.5 hour
  5. customThe product was then purified by preparative HPLC (Gradient 0-70% Acetonitrile/0.1% aq. TFA)

出典と根拠

ORDレコード
ord-0846486d44fd4fddbad2b57d35bc9362
出典データセット
uspto-grants-2004_03
特許番号
US06699860B2

反応ノート

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