Hydrochloric Acid → Tert-butyl(+/-)-4-(1-amino-3-methylbutyl)benzoate

HRID 1424285Notes

Reaction equation

HRID 1424285 reaction equation
[CH3:1][CH:2]([CH3:19])[CH2:3][C:4]([C:6]1[CH:18]=[CH:17][C:9]([C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])=[CH:8][CH:7]=1)=O.C([O-])(=O)C.[NH4+].C([BH3-])#[N:26].[Na+].Cl>CO>[NH2:26][CH:4]([C:6]1[CH:18]=[CH:17][C:9]([C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])=[CH:8][CH:7]=1)[CH2:3][CH:2]([CH3:19])[CH3:1]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 517165Ammonium AcetateHCID 5003444Sodium cyanoborohydrideHCID 71239698Tert-butyl 4-(3-methylbutanoyl)benzoate

Product 1

HCID 71243809Tert-butyl(+/-)-4-(1-amino-3-methylbutyl)benzoate

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of tert-butyl 4-(3-methylbutanoyl)benzoate (500 mg, 1.91 mmol) and ammonium acetate (1.50 g, 19.1 mmol) in methanol (9.5 mL) was added sodium cyanoborohydride (189 mg, 2.86 mmol). The mixture was heated to 60° C. for 21 hours, then cooled to room temperature. 1 N hydrochloric acid (7 mL) was added dropwise. After 1 hour, the mixture was concentrated under reduced pressure to remove methanol. 1 N sodium hydroxide (10 mL) was added, and the mixture was extracted with dichloromethane (3×25 mL). The combined organics were washed with sat. aq sodium chloride (15 mL), dried over anhydrous Na2SO4, and filtered, and the filtrate was concentrated. Purification by silica gel flash chromatography (methanol/dichloromethane) gave tert-butyl(+/−)-4-(1-amino-3-methylbutyl)benzoate as a colorless oil. 1H NMR (400 MHz, CDCl3) δ 7.99-7.94 (m, 2H), 7.41-7.37 (m, 2H), 4.08-4.01 (m, 1H), 1.60 (s, 9H), 1.59-1.43 (m, 3H), 0.92 (d, J=6.5 Hz, 3H), 0.90 (d, J=6.3 Hz, 3H).

Workup

  1. temperaturecooled to room temperature
  2. concentrationthe mixture was concentrated under reduced pressure
  3. customto remove methanol
  4. addition1 N sodium hydroxide (10 mL) was added
  5. extractionthe mixture was extracted with dichloromethane (3×25 mL)
  6. washThe combined organics were washed with sat. aq sodium chloride (15 mL)
  7. dry with materialdried over anhydrous Na2SO4
  8. filtrationfiltered
  9. concentrationthe filtrate was concentrated
  10. customPurification by silica gel flash chromatography (methanol/dichloromethane)

Sources & evidence

ORD record
ord-394db6a4893149f2a86bcdad7e21a778
Source dataset
uspto-grants-2015_01
Patent number
US08927577B2

Reaction notes

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