4-Toluenesulfonyl chloride → N-tert-Butoxycarbonyl-cis-4-p-Toluenesulfonyloxy-L-Proline 3-Quinolylamide

HRID 2185400Notes

Reaction equation

HRID 2185400 reaction equation
[C:1]1([CH3:11])[CH:6]=[CH:5][C:4]([S:7](Cl)(=[O:9])=[O:8])=[CH:3][CH:2]=1.[N:12]1[C:21]2[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=2)[CH:15]=[C:14]([NH:22][C:23](=[O:37])[C@@H:24]2[CH2:28][C@H:27]([OH:29])[CH2:26][N:25]2[C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31])[CH:13]=1>CN(C)C1C=CN=CC=1.ClCCl>[N:12]1[C:21]2[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=2)[CH:15]=[C:14]([NH:22][C:23](=[O:37])[C@@H:24]2[CH2:28][C@H:27]([O:29][S:7]([C:4]3[CH:5]=[CH:6][C:1]([CH3:11])=[CH:2][CH:3]=3)(=[O:9])=[O:8])[CH2:26][N:25]2[C:30]([O:32][C:33]([CH3:34])([CH3:36])[CH3:35])=[O:31])[CH:13]=1

Participants

5

Reactant 2

HCID 73974-Toluenesulfonyl chloride3×HCID 53656843N-tert-Butoxycarbonyl-cis-4-Hydroxy-L-Proline 3-Quinolylamide

Product 1

HCID 88192207N-tert-Butoxycarbonyl-cis-4-p-Toluenesulfonyloxy-L-Proline 3-QuinolylamideYield 98.3%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalyst3×HCID 6344DichloromethaneSolvent

Procedure

4-Dimethylaminopyridine (395 mg) and p-toluenesulfonyl chloride (468 mg) were added to a solution of N-tert-butoxycarbonyl-cis-4-hydroxy-L-proline 3-quinolylamide (B, 572 mg) in dichloromethane (10 mL) at 0° C. After stirring at room temperature for 2.5 hr, additional 4-dimethylaminopyridine (399 mg) and p-toluenesulfonyl chloride (465 mg) were added. Additional 4-dimethylaminopyridine (400 mg) and p-toluenesulfonyl chloride (467 mg) were added again after 2 hr. The resulting solution was stirred at room temperature for 14 hr, and the solvent was evaporated in vacuo. The residue was diluted with ethyl acetate, and washed with 0.5 M citric acid, saturated sodium hydrogen carbonate, and brine. The organic layer was dried over anhydrous sodium sulfate and evaporated in vacuo. The residue was purified by silica gel column chromatography (chloroform then chloroform:methanol=50:1, v/v) to afford the title compound (805 mg) as a pale yellow sticky oil: 1H NMR (400 MHz, CD3OD) δ 1.3-1.5 (m, 9H), 2.23 (m, 3H), 2.3-2.7 (m, 2H), 3.4-3.8 (m, 2H), 4.5 (m, 1H), 5.25 (m, 1H), 7.20 (m, 2H), 7.7-7.9 (m, 5H), 8.00 (d, 1H), 8.58 (br s, 1H), and 8.85 (br s, 1H).

Workup

  1. stirringThe resulting solution was stirred at room temperature for 14 hr
  2. customthe solvent was evaporated in vacuo
  3. additionThe residue was diluted with ethyl acetate
  4. washwashed with 0.5 M citric acid, saturated sodium hydrogen carbonate, and brine
  5. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  6. customevaporated in vacuo
  7. customThe residue was purified by silica gel column chromatography (chloroform

Sources & evidence

ORD record
ord-6303df928d05452fa65727cf45d2d18d
Source dataset
uspto-grants-2002_06
Patent number
US06399629B1

Reaction notes

Loading…