(2S,4R) Fmoc-4-amino-1-boc-pyrrolidine-2-carboxylic acid → 4-Amino-1-(tert-butoxycarbonyl)pyrrolidine-2-carboxylic acid
反応式
[C:1]([C@@:18]1(C(O)=O)[CH2:22][C@@H:21]([NH2:23])[CH2:20][N:19]1[C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])([O:3]CC1C2C(=CC=CC=2)C2C1=CC=CC=2)=[O:2]>C(#N)C.N1CCCC1>[NH2:23][CH:21]1[CH2:20][N:19]([C:24]([O:26][C:27]([CH3:28])([CH3:29])[CH3:30])=[O:25])[CH:18]([C:1]([OH:3])=[O:2])[CH2:22]1参加物
実験手順
To a solution of (2S,4R) Fmoc-4-amino-1-boc-pyrrolidine-2-carboxylic acid (400 mg, 0.884 mmol) in acetonitrile (15 mL), five drops of pyrrolidine was added. The reaction mixture was stirred at rt for 3 hr. Then it was concentrated and put on high vacuum to give crude 4-amino-1-boc-pyrrolidine-2-carboxylic acid. In another round-bottomed flask, a solution of Pd2dba3 (40 mg, 5% mol) and racemic-BINAP (56 mg, 10% mol) was stirred under nitrogen in degassed toluene (8 mL) at rt for 1 h. Then 1-chloroisoquinoline (216 mg, 1.326 mmol) and sodium t-butoxide (340 mg, 3.536 mmol) were added and the reaction mixture was stirred for 30 min. Then 4-amino-1-boc-pyrrolidine-2-carboxylic acid was added and the reaction mixture was heated under reflux for 1 h. Water was added to quench the reaction and the aqueous layer was separated and filtered through filter paper. It was then concentrated and purified by Prep. HPLC to give coupled product as TFA salt. (165 mg, 40% yield) 1H NMR (CD3OD, 400 MHz) δ 1.44 (m, 9H), 2.51-2.74 (m, 2H), 3.64 (m, 1H), 4.01 (m, 1H), 4.49 (m, 1H), 4.64 (m, 1H), 7.30 (d, J=6.85 Hz, 1H), 7.58 (d, J=6.85 Hz, 1H), 7.79 (m, 1H), 7.91-7.99 (m, 2H), 8.56 (d, J=8.56 Hz, 1H). MS m/z 358 (MH+).
後処理
- concentrationThen it was concentrated
出典と根拠
- ORDレコード
- ord-7db9bc8c73c947a690a1988e69fcfb12
- 出典データセット
- uspto-grants-2010_06
- 特許番号
- US07741281B2
反応ノート
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