Quinoline → (2S,4R)-Pyrrolidin-1-yl-[2-(2,4,5-trifluoro-benzyloxymethyl)-4-tritylsulfanyl-pyrrolidin-1-yl]-methanone

HRID 1006828Notes

Reaction equation

HRID 1006828 reaction equation
ClC(O[C:6](Cl)=[O:7])(Cl)Cl.[N:9]1[C:18]2[C:13](=CC=CC=2)[CH:12]=[CH:11]C=1.[F:19][C:20]1[CH:53]=[C:52]([F:54])[C:51]([F:55])=[CH:50][C:21]=1[CH2:22][O:23][CH2:24][C@@H:25]1[CH2:29][C@@H:28]([S:30][C:31]([C:44]2[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=2)([C:38]2[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=2)[C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)[CH2:27][NH:26]1.N1CCCC1>C(Cl)Cl>[N:9]1([C:6]([N:26]2[CH2:27][C@H:28]([S:30][C:31]([C:38]3[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=3)([C:32]3[CH:33]=[CH:34][CH:35]=[CH:36][CH:37]=3)[C:44]3[CH:45]=[CH:46][CH:47]=[CH:48][CH:49]=3)[CH2:29][C@H:25]2[CH2:24][O:23][CH2:22][C:21]2[CH:50]=[C:51]([F:55])[C:52]([F:54])=[CH:53][C:20]=2[F:19])=[O:7])[CH2:11][CH2:12][CH2:13][CH2:18]1

Participants

6

Reactant 4

HCID 7047QuinolineHCID 10426DiphosgeneHCID 31268PyrrolidineHCID 11398267(2S,4R)-2-(2,4,5-trifluoro-benzyloxymethyl)-4-tritylsulfanyl-pyrrolidine

Product 1

HCID 69430562(2S,4R)-Pyrrolidin-1-yl-[2-(2,4,5-trifluoro-benzyloxymethyl)-4-tritylsulfanyl-pyrrolidin-1-yl]-methanoneYield 109%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

A solution of 0.02 ml (0.18 mmol) trichloromethylchloroformate in 3 ml CH2Cl2 was treated at 0° C. with 0.04 ml (0.37 mmol) quinoline and after 15 min with 0.17 g (0.33 mmol) (2S,4R)-2-(2,4,5-trifluoro-benzyloxymethyl)-4-tritylsulfanyl-pyrrolidine in 2 ml CH2Cl2. After 2 h, the reaction was evaporated and redissolved in 15 ml CH2Cl2 and treated at 0° C. with 0.14 ml (1.65 mmol) pyrrolidine and stirred for 30 min. The reaction was extracted with aqueous 10% KHSO4/Et2O (3×) and the organic phase was dried over Na2SO4. Evaporation and precipitation from Et2O/pentane gave 121 mg (59%) (2S,4R)-Pyrrolidin-1-yl-[2-(2,4,5-trifluoro-benzyloxymethyl)-4-tritylsulfanyl-pyrrolidin-1-yl]-methanone, MS: 617 (M+H+).

Workup

  1. customthe reaction was evaporated
  2. dissolutionredissolved in 15 ml CH2Cl2
  3. extractionThe reaction was extracted with aqueous 10% KHSO4/Et2O (3×)
  4. dry with materialthe organic phase was dried over Na2SO4
  5. customEvaporation and precipitation from Et2O/pentane

Sources & evidence

ORD record
ord-9117e9528c69483ba3c898091f5de4d1
Source dataset
uspto-grants-2004_09
Patent number
US06790860B2

Reaction notes

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