Pyrrolidine → 3,5-Dimethyl-4-(pyrrolidin-1-ylmethyl)phenol

HRID 1159429Notes

Reaction equation

HRID 1159429 reaction equation
[CH3:1][C:2]1[CH:9]=[C:8]([OH:10])[CH:7]=[C:6]([CH3:11])[C:3]=1[CH:4]=O.[NH:12]1[CH2:16][CH2:15][CH2:14][CH2:13]1>C(Cl)Cl>[CH3:1][C:2]1[CH:9]=[C:8]([OH:10])[CH:7]=[C:6]([CH3:11])[C:3]=1[CH2:4][N:12]1[CH2:16][CH2:15][CH2:14][CH2:13]1

Participants

4

Reactant 2

HCID 31268PyrrolidineHCID 5910722,6-Dimethyl-4-hydroxybenzaldehyde

Product 1

HCID 686199633,5-Dimethyl-4-(pyrrolidin-1-ylmethyl)phenolYield 33%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a stirring solution of 2,6-dimethyl-4-hydroxybenzaldehyde (8.2 g, 52.1 mmol) in methylene chloride (80 mL) at 0 C (ice/water bath) was added pyrrolidine (6.5 mL, 78.1 mmol) followed by Na(Oac)3BH and then the reaction was warmed to rt. After 2 hr the reaction was quenched with 1 N NaOH and extracted with methylene chloride. The combined organic layers were dried over MgSO4, filtered and concentrated. This material was triterated with diethyl ether and filtered. The filtrate was concentrated and chromatographed by flash column chromatography using a 330 g ISCO column, eluting with a gradient of 10%, 20%, 30%, 50% MeOH/CHCl3. The product containing fractions were collected and concentrated to give the title compound (3.5 g, 33% yield) as a yellow solid. LCMS-data: 392.2, and 206.3 (M+H)+ (calculated for C13H19NO 205.3). 1H NMR data (CDCl3): 7.52 (bs, 1H), 6.17 (s, 2H), 3.57 (s, 2H), 2.67-2.61 (m, 4H), 2.25 (s, 6H), 1.82-1.72 (m, 4H); C13 NMR δ 155.2, 139.0, 127.4, 116.2, 54.8, 53.0, 23.4, 20.5.

Workup

  1. customAfter 2 hr the reaction was quenched with 1 N NaOH
  2. extractionextracted with methylene chloride
  3. dry with materialThe combined organic layers were dried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. filtrationfiltered
  7. concentrationThe filtrate was concentrated
  8. customchromatographed by flash column chromatography
  9. washeluting with a gradient of 10%, 20%, 30%, 50% MeOH/CHCl3
  10. additionThe product containing fractions
  11. customwere collected
  12. concentrationconcentrated

Sources & evidence

ORD record
ord-34b571bfe6df40a7848e941eacdb304f
Source dataset
uspto-grants-2010_10
Patent number
US07812040B2

Reaction notes

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