Pyridine → (2S,4R)-2-(2,4,5-trifluoro-benzyloxymethyl)-4-tritylsulfanyl-pyrrolidine-1-carboxylic acid 2-fluoro-phenyl ester

HRID 458350Notes

Reaction equation

HRID 458350 reaction equation
Cl[C:2]([O:5][C:6](Cl)=[O:7])(Cl)Cl.[F:9][C:10]1C=[CH:14][CH:13]=[CH:12][C:11]=1O.N1C2C(=CC=CC=2)C=CC=1.[F:27][C:28]1[CH:61]=[C:60]([F:62])[C:59]([F:63])=[CH:58][C:29]=1[CH2:30][O:31][CH2:32][C@@H:33]1[CH2:37][C@@H:36]([S:38][C:39]([C:52]2[CH:57]=[CH:56][CH:55]=[CH:54][CH:53]=2)([C:46]2[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=2)[C:40]2[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=2)[CH2:35][NH:34]1.N1C=CC=CC=1>C(Cl)Cl.CN(C1C=CN=CC=1)C>[F:9][C:10]1[CH:11]=[CH:12][CH:13]=[CH:14][C:2]=1[O:5][C:6]([N:34]1[CH2:35][C@H:36]([S:38][C:39]([C:46]2[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=2)([C:40]2[CH:41]=[CH:42][CH:43]=[CH:44][CH:45]=2)[C:52]2[CH:53]=[CH:54][CH:55]=[CH:56][CH:57]=2)[CH2:37][C@H:33]1[CH2:32][O:31][CH2:30][C:29]1[CH:58]=[C:59]([F:63])[C:60]([F:62])=[CH:61][C:28]=1[F:27])=[O:7]

Participants

8

Reactant 5

HCID 1049PyridineHCID 7047QuinolineHCID 97072-FluorophenolHCID 10426DiphosgeneHCID 11398267(2S,4R)-2-(2,4,5-trifluoro-benzyloxymethyl)-4-tritylsulfanyl-pyrrolidine

Product 1

HCID 69432551(2S,4R)-2-(2,4,5-trifluoro-benzyloxymethyl)-4-tritylsulfanyl-pyrrolidine-1-carboxylic acid 2-fluoro-phenyl esterYield 60%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent2×

Procedure

A solution of 0.19 ml (1.58 mmol) trichloromethyl-chloroformate in 20 ml CH2Cl2 was treated at 0° C. with 0.28 ml (3 mmol) 2-fluorophenol and 0.35 ml (3 mmol) quinoline and then stirred for 3 h at room temperature. The reaction was then cooled (0° C.) and a solution of 0.52 g (1 mmol) (2S,4R)-2-(2,4,5-trifluoro-benzyloxymethyl)-4-tritylsulfanyl-pyrrolidine and 0.2 ml (2.5 mmol) pyridine in 3 ml CH2Cl2 was added, followed by 122 mg (1 mmol) DMAP. After 3 h at 0° C. the reaction was evaporated and poured into aqueous 10% KHSO4/Et2O (3×). The organic phases were washed with aqueous 10% NaCl solution, dried over Na2SO4 and evaporated. Flash chromatography on silica gel (hexane/EtOAc 9:1) gave 0.39 g (60%) (2S,4R)-2-(2,4,5-trifluoro-benzyloxymethyl)-4-tritylsulfanyl-pyrrolidine-1-carboxylic acid 2-fluoro-phenyl ester, MS: 658 (MH+).

Workup

  1. temperatureThe reaction was then cooled (0° C.)
  2. customAfter 3 h at 0° C. the reaction was evaporated
  3. additionpoured into aqueous 10% KHSO4/Et2O (3×)
  4. washThe organic phases were washed with aqueous 10% NaCl solution
  5. dry with materialdried over Na2SO4
  6. customevaporated

Sources & evidence

ORD record
ord-4d7d4d52dd1840b19e1f4b6bde2c9321
Source dataset
uspto-grants-2007_03
Patent number
US07189756B2

Reaction notes

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