Isoquinoline, 1-chloro- → 4-(Isoquinolin-1-yloxy)-pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester

HRID 719836

反応式

HRID 719836 の反応式
[CH3:1][C:2]([O:5][C:6]([N:8]1[C@H:12]([C:13]([OH:15])=[O:14])[CH2:11][CH:10]([OH:16])[CH2:9]1)=[O:7])([CH3:4])[CH3:3].CC([O-])(C)C.[K+].Cl[C:24]1[C:33]2[C:28](=[CH:29][CH:30]=[CH:31][CH:32]=2)[CH:27]=[CH:26][N:25]=1.CO.C(Cl)Cl>CS(C)=O>[C:2]([O:5][C:6]([N:8]1[CH2:9][CH:10]([O:16][C:24]2[C:33]3[C:28](=[CH:29][CH:30]=[CH:31][CH:32]=3)[CH:27]=[CH:26][N:25]=2)[CH2:11][CH:12]1[C:13]([OH:15])=[O:14])=[O:7])([CH3:1])([CH3:3])[CH3:4]

参加物

6

反応物 4

HCID 140539Isoquinoline, 1-chloro-HCID 111389801-(1,1-Dimethylethyl) (2S)-4-hydroxy-1,2-pyrrolidinedicarboxylateHCID 21226129Dichloromethane methanolHCID 23665647Potassium tert-butoxide

生成物 1

HCID 235952584-(Isoquinolin-1-yloxy)-pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester収率 96%

試薬・触媒・溶媒 1

HCID 679Dimethyl Sulfoxide溶媒

実験手順

A suspension of Boc-L-4-hydroxyproline (N-Boc(2S,4R)-hydroxyproline) (3.85 g 16.6 millimole (“mmol”) (CHEM-IMPEX International) in DMSO (60 mL) was cooled in an ice bath for ˜3 minutes, and then t-BuOK (4.66 g, 41.5 mmol) was added. Stirring and cooling in the ice bath was continued for a few minutes until a solid mass formed. At this time the reaction mixture was allowed to warm to rt over 1.5 h to give a clear colorless solution. 1-Chloroisoquinoline (3.0 g, 18.3 mmol) was added in two portions 10 min apart. The reaction was stirred for 24 h at rt. The dark reaction mixture was partitioned between ether (200 mL) and water (600 mL). The aqueous phase was acidified to pH 4 using 4N HCl. The resulting milky yellow solution was extracted with ether (4×200 mL). The combined ether extracts were dried (MgSO4), filtered, and concentrated in vacuo to give a golden oil. Flash chromatography (2–4% MeOH/CH2Cl2) gave 5.69 g (96%) of 4-(isoquinolin-1-yloxy)-pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester as an off-white solid: LC-MS (Method A, retention time: 3.06 min), MS m/z 359 (M++1).

後処理

  1. temperaturewas cooled in an ice bath for ˜3 minutes
  2. waitwas continued for a few minutes until a solid mass
  3. customformed
  4. customto give a clear colorless solution
  5. stirringThe reaction was stirred for 24 h at rt
  6. customThe dark reaction mixture
  7. customwas partitioned between ether (200 mL) and water (600 mL)
  8. extractionThe resulting milky yellow solution was extracted with ether (4×200 mL)
  9. dry with materialThe combined ether extracts were dried (MgSO4)
  10. filtrationfiltered
  11. concentrationconcentrated in vacuo
  12. customto give a golden oil

出典と根拠

ORDレコード
ord-9b8ea242cdab46fa8f983a5c027513b3
出典データセット
uspto-grants-2006_11
特許番号
US07132504B2

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