Acetyl chloride → (3R,5S)-Thioacetic acid S-[1-(5-propyl-pyrimidin-2-yl)-5-(2,4,5-trifluoro-benzyloxymethyl)-pyrrolidin-3-yl] ester

HRID 431833Notes

Reaction equation

HRID 431833 reaction equation
[CH2:1]([C:4]1[CH:5]=[N:6][C:7]([N:10]2[C@H:14]([CH2:15][O:16][CH2:17][C:18]3[CH:23]=[C:22]([F:24])[C:21]([F:25])=[CH:20][C:19]=3[F:26])[CH2:13][C@@H:12]([SH:27])[CH2:11]2)=[N:8][CH:9]=1)[CH2:2][CH3:3].F[C:29](F)(F)[C:30]([O-])=[O:31].C(Cl)(=O)C>C([O-])(O)=O.[Na+].CCOC(C)=O.N1C=CC=CC=1>[CH2:1]([C:4]1[CH:5]=[N:6][C:7]([N:10]2[C@H:14]([CH2:15][O:16][CH2:17][C:18]3[CH:23]=[C:22]([F:24])[C:21]([F:25])=[CH:20][C:19]=3[F:26])[CH2:13][C@@H:12]([S:27][C:30](=[O:31])[CH3:29])[CH2:11]2)=[N:8][CH:9]=1)[CH2:2][CH3:3]

Participants

6

Reactant 3

HCID 6367Acetyl chlorideHCID 84468TrifluoroacetateHCID 10164542(3r,5s)-1-(5-Propyl-pyrimidin-2-yl)-5-(2,4,5-trifluoro-benzyloxymethyl)-pyrrolidine-3-thiol

Product 1

HCID 91284815(3R,5S)-Thioacetic acid S-[1-(5-propyl-pyrimidin-2-yl)-5-(2,4,5-trifluoro-benzyloxymethyl)-pyrrolidin-3-yl] esterYield 87%

Reagents, catalysts & solvents 2

HCID 1049PyridineSolventHCID 86584982Sodium bicarbonate ethyl acetateSolvent

Procedure

A solution of 397 mg (1 mmol) (3R,5S)-1-(5-Propyl-pyrimidin-2-yl)-5-(2,4,5-trifluoro-benzyloxymethyl)-pyrrolidine-3-thiol (the trifluoro-acetate salt was extracted with aqueous saturated NaHCO3/EtOAc) in 6 ml pyridine were treated at 0° C. with 0.14 ml (2 mmol) acetyl chloride and stirred for 5 h at RT. The reaction was poured on ice water and extracted wit Et2O (3×). The organic phases were washed with aqueous 1 N HCl and 10% NaCl, dried (Na2SO4) and evaporated. Flash chromatography on silica gel (CH2Cl2/Et2O 100:0 to 95:5) gave 383 mg (87%) (3R,5S)-Thioacetic acid S-[1-(5-propyl-pyrimidin-2-yl)-5-(2,4,5-trifluoro-benzyloxymethyl)-pyrrolidin-3-yl]ester, MS: 440 (MH+).

Workup

  1. additionThe reaction was poured on ice water
  2. extractionextracted wit Et2O (3×)
  3. washThe organic phases were washed with aqueous 1 N HCl and 10% NaCl
  4. dry with materialdried (Na2SO4)
  5. customevaporated

Sources & evidence

ORD record
ord-3271d5ddf4f2488ab54f084bd007ac03
Source dataset
uspto-grants-2003_12
Patent number
US06660738B2

Reaction notes

Loading…