Methyl 4-Formylbenzoate → Methyl 4-(pyrrolidin-1-ylmethyl)benzoate

HRID 1771076Notes

Reaction equation

HRID 1771076 reaction equation
[NH:1]1[CH2:5][CH2:4][CH2:3][CH2:2]1.[CH:6]([C:8]1[CH:17]=[CH:16][C:11]([C:12]([O:14][CH3:15])=[O:13])=[CH:10][CH:9]=1)=O.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>ClCCCl.[OH-].[Na+]>[N:1]1([CH2:6][C:8]2[CH:17]=[CH:16][C:11]([C:12]([O:14][CH3:15])=[O:13])=[CH:10][CH:9]=2)[CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

6

Reactant 3

HCID 15294Methyl 4-FormylbenzoateHCID 31268PyrrolidineHCID 5049666Sodium triacetoxyborohydride

Product 1

HCID 756589Methyl 4-(pyrrolidin-1-ylmethyl)benzoateYield 50%

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolventHCID 14798Sodium HydroxideSolvent

Procedure

Pyrrolidine (0.12 mL, 1.52 mmol), methyl 4-formylbenzoate (0.250 g, 1.52 mmol), NaBH(OAc)3 (0.52 g, 2.4 mmol) and 5 Å molecular sieves were dissolved in 1,2-dichloroethane (5 mL) under Ar atmosphere and stirred for 24 h at RT. Then, the reaction was diluted with 2 N NaOH (30 mL) and extracted with EtOAc (3×20 mL). The combined organic fractions were washed with brine (15 mL), dried over Na2SO4, filtered and concentrated in vacuo. The crude product was purified via automated column chromatography (50-100% EtOAc/hexane, 25 g cartridge) to yield the title compound as a clear oil (0.166 g, 50%). 1H NMR (400 MHz, CDCl3): δ 8.00 (d, J=8.0 Hz, 2H), 7.43 (d, J=8.0 Hz, 2H), 3.92 (s, 3H), 3.69 (s, 2H), 2.54 (br, 4H), 1.81 (t, J=3.2 Hz, 4H).

Workup

  1. extractionextracted with EtOAc (3×20 mL)
  2. washThe combined organic fractions were washed with brine (15 mL)
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe crude product was purified

Sources & evidence

ORD record
ord-bd8b9de901da4f698102af0695a60012
Source dataset
uspto-grants-2016_02
Patent number
US09249087B2

Reaction notes

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