Carbon Dioxide → HCID 69926904, compound
Reaction equation
[F:1][CH:2]([CH2:6][CH2:7][C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:3]([OH:5])=O.C(N1C=CN=C1)(N1C=CN=C1)=O.C(=O)=O.C(N(CC)CC)C.FC(F)(F)C(O)=O.[NH:43]1[CH2:47][CH2:46][C@@H:45]([S:48][C:49]2[CH:54]=[CH:53][C:52]([OH:55])=[CH:51][CH:50]=2)[CH2:44]1>CN(C=O)C>[F:1][CH:2]([CH2:6][CH2:7][C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:3]([N:43]1[CH2:47][CH2:46][C@@H:45]([S:48][C:49]2[CH:54]=[CH:53][C:52]([OH:55])=[CH:51][CH:50]=2)[CH2:44]1)=[O:5]Participants
Conditions
- Temperature
- 55 °C
Procedure
(RS)-2-Fluoro-4-phenyl-butyric acid (0.66 g, 3.63 mmol) was dissolved in DMF (5 ml) and carbonyldiimidazole (0.64 g, 3.8 mmol) was added portionwise. After evolution of CO2 has ceased, the reaction mixture was warmed to 55° C. for 20 minutes and then cooled to room temperature. A mixture of triethylamine (0.46 ml, 3.3 mmol) and (3R)-4-(pyrrolidin-3-ylsulfanyl)-phenol trifluoroacetic acid (1.02 g, 3.3 mmol) in DMF (5 ml) was added. The mixture was stirred at room temperature for 2 hours. The solvent was removed in vacuo and the residue taken up in H2O (30 ml).The mixture was extracted with ethylacetate (3×20 ml). The combined organic phases were dried over Na2SO4, filtered and the solvent was removed in vacuo. The residue was chromatographed over silica gel (CH2Cl2—MeOH, 99:1) to provide (2RS,3R)-2-fluoro-1-[3-(4-hydroxy-phenylsulfanyl)-pyrrolidin-1-yl]-4-phenyl-butan-1-one (1.12 g, 95%) as light yellow oil, MS: m/e=359.1(M+).
Workup
- temperaturecooled to room temperature
- additionwas added
- customThe solvent was removed in vacuo
- extractionwas extracted with ethylacetate (3×20 ml)
- dry with materialThe combined organic phases were dried over Na2SO4
- filtrationfiltered
- customthe solvent was removed in vacuo
- customThe residue was chromatographed over silica gel (CH2Cl2—MeOH, 99:1)
Sources & evidence
- ORD record
- ord-a6ce16e2ccac4297b92bc16b472b3772
- Source dataset
- uspto-grants-2002_09
- Patent number
- US06451819B2
Reaction notes
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