Sodium borohydride → (2R,4R)-4-(tert-butyldimethylsilyloxy)-2-(3-fluorophenyl)pyrrolidine

HRID 1631323Notes

Reaction equation

HRID 1631323 reaction equation
[Si:1]([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:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[BH4-].[Na+]>CO.CC(O)=O>[Si:1]([O:8][C@H:9]1[CH2:10][NH:11][C@@H:12]([C:14]2[CH:19]=[CH:18][CH:17]=[C:16]([F:20])[CH:15]=2)[CH2:13]1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2]

Participants

5

Reactant 2

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

Product 1

HCID 66684536(2R,4R)-4-(tert-butyldimethylsilyloxy)-2-(3-fluorophenyl)pyrrolidineYield 77.1%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 887MethanolSolvent

Conditions

Temperature
-78 °C

Procedure

(R)-3-(tert-butyldimethylsilyloxy)-5-(3-fluorophenyl)-3,4-dihydro-2H-pyrrole (6.21 g, 21.2 mmol) was dissolved in methanol (100 mL) and AcOH (10 mL). The reaction was cooled to −78° C. and the sodium borohydride (2.00 g, 52.9 mmol) was slowly added in small portions. The reaction was allowed to warm to ambient temperature overnight. The reaction mixture was concentrated and the residue was diluted with EtOAc and 1N NaOH. Additional NaOH pellets were added to basify the aqueous layer. The organic layer was separated and the aqueous layer was extracted with EtOAc. The combined organic layers were dried with MgSO4, filtered and concentrated. The residual oil was purified by silica chromatography eluting with 5% MeOH/EtOAc to afford (2R,4R)-4-(tert-butyldimethylsilyloxy)-2-(3-fluorophenyl)pyrrolidine (4.82 g, 77.1%) as a brown oil. MS (apci) m/z=296.1 (M+H).

Workup

  1. temperatureto warm to ambient temperature overnight
  2. concentrationThe reaction mixture was concentrated
  3. additionthe residue was diluted with EtOAc and 1N NaOH
  4. additionAdditional NaOH pellets were added
  5. customThe organic layer was separated
  6. extractionthe aqueous layer was extracted with EtOAc
  7. dry with materialThe combined organic layers were dried with MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe residual oil was purified by silica chromatography
  11. washeluting with 5% MeOH/EtOAc

Sources & evidence

ORD record
ord-ee43d459aefe45b1a1d6fa837fe82f86
Source dataset
uspto-grants-2014_07
Patent number
US08791123B2

Reaction notes

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