3-Aminoquinoline → trans-4-Hydroxy-N-tert-Butoxycarbonyl-L-Proline 3-Quinolylamide

HRID 2185398Notes

Reaction equation

HRID 2185398 reaction equation
O=C1N(P(Cl)(N2CCOC2=O)=O)CCO1.[OH:16][C@H:17]1[CH2:21][N:20]([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[C@H:19]([C:29]([OH:31])=O)[CH2:18]1.[NH2:32][C:33]1[CH:34]=[N:35][C:36]2[C:41]([CH:42]=1)=[CH:40][CH:39]=[CH:38][CH:37]=2.C(N(C(C)C)CC)(C)C>ClCCl>[N:35]1[C:36]2[C:41](=[CH:40][CH:39]=[CH:38][CH:37]=2)[CH:42]=[C:33]([NH:32][C:29](=[O:31])[C@@H:19]2[CH2:18][C@@H:17]([OH:16])[CH2:21][N:20]2[C:22]([O:24][C:25]([CH3:26])([CH3:27])[CH3:28])=[O:23])[CH:34]=1

Participants

6

Reactant 4

HCID 113753-AminoquinolineHCID 81531DiisopropylethylamineHCID 88804(2S,4R)-4-hydroxy-1-[(2-methylpropan-2-yl)oxycarbonyl]pyrrolidine-2-carboxylic acidHCID 152842Bis(2-oxo-3-oxazolidinyl)phosphinic chloride

Product 1

HCID 70176198trans-4-Hydroxy-N-tert-Butoxycarbonyl-L-Proline 3-QuinolylamideYield 109.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Bis(2-oxo-3-oxazolidinyl)phosphinic chloride (5.72 g) was added to a solution of trans-4-hydroxy-N-tert-butoxycarbonyl-L-proline (3.47 g), 3-aminoquinoline (2.17 g), and diisopropylethylamine (5 mL) in dichloromethane (100 mL) at 0° C. After stirring at room temperature for 45 hr, the solvent was removed in vacuo. Ethyl acetate (500 mL) and 2 N sodium carbonate (500 mL) were added to the residue. The separated organic layer was washed with brine, dried over anhydrous sodium sulfate, and evaporated in vacuo. The residue was purified by silica gel column chromatography (chloroform:methanol=50:1 to 30:1, 20:1, and 10:1, v/v) to afford the title compound (5.85 g) as a colorless sticky oil: 1H NMR (400 MHz, CD3OD) δ 1.3-1.5 (m, 9H), 2.1-2.2 (m, 1H), 2.3-2.4 (m, 1H), 3.5-3.7 (m, 2H), 4.4-4.6 (m, 2), 7.61 (m, 1H), 7.69 (m, 1H), 7.88 (m, 1H), 7.97 (m, 1H), 8.71-8.76 (m, 1H), and 8.93-8.94 (m, 1H).

Workup

  1. customthe solvent was removed in vacuo
  2. additionEthyl acetate (500 mL) and 2 N sodium carbonate (500 mL) were added to the residue
  3. washThe separated organic layer was washed with brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. customevaporated in vacuo
  6. customThe residue was purified by silica gel column chromatography (chloroform

Sources & evidence

ORD record
ord-de64d044ea6f46c1a0d0835b208e6237
Source dataset
uspto-grants-2002_06
Patent number
US06399629B1

Reaction notes

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