Methanol → HCID 10291255, compound

HRID 1280727Notes

Reaction equation

HRID 1280727 reaction equation
[F:1][CH:2]([CH2:18][CH2:19][C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1)[C:3]([N:5]1[CH2:9][CH2:8][C@H:7]([S:10][C:11]2[CH:16]=[CH:15][C:14]([OH:17])=[CH:13][CH:12]=2)[CH2:6]1)=O.CO>C1COCC1>[F:1][CH:2]([CH2:18][CH2:19][C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1)[CH2:3][N:5]1[CH2:9][CH2:8][C@H:7]([S:10][C:11]2[CH:16]=[CH:15][C:14]([OH:17])=[CH:13][CH:12]=2)[CH2:6]1

Participants

4

Reactant 2

HCID 887MethanolHCID 69927330HCID 69927330, compound

Product 1

HCID 10291255HCID 10291255, compoundYield 70%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

(2RS,3S)-2-Fluoro-1-[3-(4-hydroxy-phenylsulfanyl)-pyrrolidin-1-yl]-4-phenyl-butan-1-one (200 mg, 0.56 mmol) was dissolved in THF (4 ml). Borane-dimethylsulfide complex (170 μl, 1.67 mmol) was added. The mixture was refluxed for 7 hours and then cooled to 0° C. MeOH (0.7 ml) was added dropwise and the solvent was removed in vacuo. The residue was dissolved with THF (3.5 ml) and 5N HCl (1.1 ml) and was stirred at 60° C. for 12 hours. The solvent was removed in vacuo and the residue was taken up in saturated NaHCO3 (3 ml). The aqueous layer was extracted with CH2Cl2 (3 times). The combined organic phases were dried over Na2SO4, filtered and the solvent was evaporated. The residue was chromatographed over silica gel (CH2Cl—MeOH, 99:1) to provide (2RS,3S)-4-[1-(2-fluoro-4-phenyl-butyl)-pyrrolidin-3-ylsulfanyl]-phenol (134 mg, 70%) as colorless oil. MS: m/e 346.3 (M+H+).

Workup

  1. additionBorane-dimethylsulfide complex (170 μl, 1.67 mmol) was added
  2. temperatureThe mixture was refluxed for 7 hours
  3. customthe solvent was removed in vacuo
  4. dissolutionThe residue was dissolved with THF (3.5 ml) and 5N HCl (1.1 ml)
  5. customThe solvent was removed in vacuo
  6. extractionThe aqueous layer was extracted with CH2Cl2 (3 times)
  7. dry with materialThe combined organic phases were dried over Na2SO4
  8. filtrationfiltered
  9. customthe solvent was evaporated
  10. customThe residue was chromatographed over silica gel (CH2Cl—MeOH, 99:1)

Sources & evidence

ORD record
ord-9930e8a356014e8587ebd789c871e295
Source dataset
uspto-grants-2002_09
Patent number
US06451819B2

Reaction notes

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