Ammonium Acetate → Ethyl(+/-)-4-(1-aminobutyl)benzoate

HRID 2281114Notes

Reaction equation

HRID 2281114 reaction equation
C([BH3-])#[N:2].[Na+].[C:5]([C:10]1[CH:20]=[CH:19][C:13]([C:14]([O:16][CH2:17][CH3:18])=[O:15])=[CH:12][CH:11]=1)(=O)[CH2:6][CH2:7][CH3:8].C([O-])(=O)C.[NH4+]>CO>[NH2:2][CH:5]([C:10]1[CH:20]=[CH:19][C:13]([C:14]([O:16][CH2:17][CH3:18])=[O:15])=[CH:12][CH:11]=1)[CH2:6][CH2:7][CH3:8]

Participants

5

Reactant 3

HCID 517165Ammonium AcetateHCID 5003444Sodium cyanoborohydrideHCID 67980577Ethyl 4-butyrylbenzoate

Product 1

HCID 71243833Ethyl(+/-)-4-(1-aminobutyl)benzoate

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
60 °C

Procedure

Sodium cyanoborohydride (29.8 g, 0.450 mol) was added to a solution of Intermediate 1 (66.1 g, 0.300 mol) and ammonium acetate (236 g, 3.00 mol) in methanol (1000 mL). The solution was fitted with a reflux condenser and heated to 60° C. for 16 h. The solution was allowed to cool to room temperature. The reaction was quenched by dropwise addition of 1N HCl (300 mL) and allowed to stir at room temperature for 1 h. The reaction mixture was concentrated to remove methanol. This mixture was diluted by careful addition of 1N NaOH (500 mL) followed by extraction with dichloromethane (3×500 mL). The combined organic layers were dried over sodium sulfate, filtered and concentrated. Purification by silica gel flash chromatography (methanol/dichloromethane) gave ethyl (+/−)-4-(1-aminobutyl)benzoate (Intermediate 2). 1H NMR (400 MHz, CDCl3) δ 8.01 (d, J=8.2 Hz, 2 H), 7.40 (d, J=8.2 Hz, 2 H), 4.38 (q, J=7.2 Hz, 2 H), 3.98 (t, J=6.9 Hz, 1 H), 1.95 (br. s., 2 H), 1.74-1.56 (m, 2 H), 1.40 (t, J=7.1 Hz, 3 H), 1.16-1.37 (m, 2 H), 0.91 (t, J=7.4 Hz, 3 H).

Workup

  1. customThe solution was fitted with a reflux condenser
  2. temperatureto cool to room temperature
  3. customThe reaction was quenched by dropwise addition of 1N HCl (300 mL)
  4. concentrationThe reaction mixture was concentrated
  5. customto remove methanol
  6. additionThis mixture was diluted by careful addition of 1N NaOH (500 mL)
  7. extractionfollowed by extraction with dichloromethane (3×500 mL)
  8. dry with materialThe combined organic layers were dried over sodium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customPurification by silica gel flash chromatography (methanol/dichloromethane)

Sources & evidence

ORD record
ord-733f59a621704bb6b5ad862f442d48e0
Source dataset
uspto-grants-2015_09
Patent number
US09139538B2

Reaction notes

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