Citric Acid → (2S,4R)-1-(tert-butoxycarbonyl)-4-(6-methoxy-3-methylisoquinolin-1-yloxy)pyrrolidine-2-carboxylic acid

HRID 1511473ノート

反応式

HRID 1511473 の反応式
[C:1]([N:8]1[CH2:15][CH:14]([OH:16])[CH2:13][C@H:9]1[C:10]([OH:12])=[O:11])([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].CC(C)([O-])C.[K+].Cl[C:24]1[C:33]2[C:28](=[CH:29][C:30]([O:34][CH3:35])=[CH:31][CH:32]=2)[CH:27]=[C:26]([CH3:36])[N:25]=1.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>CS(C)=O>[C:4]([O:3][C:1]([N:8]1[CH2:15][C@H:14]([O:16][C:24]2[C:33]3[C:28](=[CH:29][C:30]([O:34][CH3:35])=[CH:31][CH:32]=3)[CH:27]=[C:26]([CH3:36])[N:25]=2)[CH2:13][C@H:9]1[C:10]([OH:12])=[O:11])=[O:2])([CH3:7])([CH3:6])[CH3:5]

参加物

6

反応物 4

HCID 311Citric AcidHCID 111389801-(1,1-Dimethylethyl) (2S)-4-hydroxy-1,2-pyrrolidinedicarboxylateHCID 23665647Potassium tert-butoxide2 回HCID 578930951-Chloro-6-methoxy-3-methylisoquinoline

生成物 1

HCID 57893088(2S,4R)-1-(tert-butoxycarbonyl)-4-(6-methoxy-3-methylisoquinolin-1-yloxy)pyrrolidine-2-carboxylic acid

試薬・触媒・溶媒 1

HCID 679Dimethyl Sulfoxide溶媒2 回

実験手順

N-BOC-4-hydroxy-L-proline (A; 281 mg; 1.21 mmol) was dissolved in dimethylsulfoxide (3 mL) at room temperature then potassium t-butoxide (270 mg; 2.4 mmol) was added. The resulting solution was stirred at room temperature for 2 hours, then cooled to 0° C. A solution of 1-chloro-6-methoxy-3-methylisoquinoline in dimethylsulfoxide (3 mL) was then added dropwise to the cold solution, followed by t-BuOK, and the mixture was allowed to warn to room temperature. The solution was stirred for 16 hours. The reaction mixture was acidified to pH=4 with 5% aq. citric acid. The solution was extracted with ethyl acetate and the organic phase washed with water followed by brine. The organic phase was concentrated under reduced pressure to give (2S,4R)-1-(tert-butoxycarbonyl)-4-(6-methoxy-3-methylisoquinolin-1-yloxy)pyrrolidine-2-carboxylic acid.

後処理

  1. temperaturecooled to 0° C
  2. customto warn to room temperature
  3. stirringThe solution was stirred for 16 hours
  4. extractionThe solution was extracted with ethyl acetate
  5. washthe organic phase washed with water
  6. concentrationThe organic phase was concentrated under reduced pressure

出典と根拠

ORDレコード
ord-c0d6882bdf8740b1b82840f7788649d4
出典データセット
uspto-grants-2012_07
特許番号
US08211897B2

反応ノート

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