Acetic Acid → (3R,5R)-5-(3-fluorophenyl)pyrrolidin-3-ol

HRID 2275337Notes

Reaction equation

HRID 2275337 reaction equation
[Si]([O:8][C@@H:9]1[CH2:13][C:12]([C:14]2[CH:19]=[CH:18][CH:17]=[C:16]([F:20])[CH:15]=2)=[N:11][CH2:10]1)(C(C)(C)C)(C)C.CC(O)=O.[BH4-].[Na+]>CO>[F:20][C:16]1[CH:15]=[C:14]([C@@H:12]2[NH:11][CH2:10][C@H:9]([OH:8])[CH2:13]2)[CH:19]=[CH:18][CH:17]=1

Participants

5

Reactant 3

HCID 176Acetic AcidHCID 4311764Sodium borohydrideHCID 66847764(R)-3-(tert-butyldimethylsilyloxy)-5-(3-fluorophenyl)-3,4-dihydro-2H-pyrrole

Product 1

HCID 67330070(3R,5R)-5-(3-fluorophenyl)pyrrolidin-3-olYield 95%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

(R)-3-(tert-butyldimethylsilyloxy)-5-(3-fluorophenyl)-3,4-dihydro-2H-pyrrole (5.0 g, 17.0 mmol) was dissolved in 50 mL methanol and 10 mL AcOH and cooled to −40° C. NaBH4 (1.6 g, 43 mmol) was slowly added in small portions. The reaction was allowed to warm to ambient temperature. Most of the solvent was removed by rotary evaporation. The reaction was taken up in 200 mL of EtOAc, washed with 1 N NaOH, and filtered through Phase Separator filter paper, and concentrated. The crude product was taken up in 20 mL of 2 N HCl in dioxane. The reaction was concentrated, taken up in 200 mL of EtOAc, washed with 1 N NaOH, filtered, and concentrated, yielding the crude product, which was carried to the next step without further purification (2.93 g, 95% yield).

Workup

  1. customMost of the solvent was removed by rotary evaporation
  2. washwashed with 1 N NaOH
  3. filtrationfiltered through Phase Separator
  4. filtrationfilter paper
  5. concentrationconcentrated
  6. concentrationThe reaction was concentrated
  7. washwashed with 1 N NaOH
  8. filtrationfiltered
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-58695662faaf43c8b998cb93ca048896
Source dataset
uspto-grants-2015_09
Patent number
US09127013B2

Reaction notes

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