Benzyl 4-Hydroxybenzoate → benzyl (S)-4-(2-amino-1-propoxy)benzoate

HRID 354507Notes

Reaction equation

HRID 354507 reaction equation
C(OC([NH:8][C@@H:9]([CH3:12])[CH2:10][OH:11])=O)(C)(C)C.O[C:14]1[CH:29]=[CH:28][C:17]([C:18]([O:20][CH2:21][C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)=[O:19])=[CH:16][CH:15]=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.CC(OC(/N=N/C(OC(C)C)=O)=O)C>C1COCC1>[NH2:8][C@@H:9]([CH3:12])[CH2:10][O:11][C:14]1[CH:29]=[CH:28][C:17]([C:18]([O:20][CH2:21][C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)=[O:19])=[CH:16][CH:15]=1

Participants

6

Reactant 4

HCID 7180Benzyl 4-HydroxybenzoateHCID 11776TriphenylphosphineHCID 5363146Diisopropyl azodicarboxylateHCID 70231031,1-Dimethylethyl N-((1S)-2-hydroxy-1-methylethyl)carbamate

Product 1

HCID 86587801benzyl (S)-4-(2-amino-1-propoxy)benzoateYield 60%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a cooled (0° C.), stirred solution of (S)-2-(N-tert-butoxycarbonylamino)-1-propanol (6.74 g, 0.04 mol), benzyl 4-hydroxybenzoate (8.78 g, 0.04 mol), and Ph3P (15.13 g, 0.06 mol) in THF (100 ml) was added DIAD (11.4 ml, 0.06 mol), and the reaction mixture was heated under reflux overnight. The solution was evaporated and the residue was dissolved in CH2Cl2 (30 ml) and TFA (30 ml). The solution was stirred at room temperature for 30 min. and the solution was concentrated in vacuo. The residue was dissolved in CHCl3, washed with sat. NaRCO3, dried over Na2SO4 and evaporated. The residue was purified by column chromatography on silica-gel with CHCl3 to CHCl3—MeOH (9:1, v/v) as eluent to give benzyl (S)-4-(2-amino-1-propoxy)benzoate (6.63 g, 2 steps, 60%) as a yellow oil. 1H-NMR (CDCl3) δ1.18 (d, J=6.3 Hz, 3 H), 3,35-3.39 (m, 1 H), 3.71-3.75 (m, 1 H), 3.90-3.93 (m, 1 H), 5.34 (s, 2 H), 6.90-6.93 (m, 2H), 7.32-7.46 (M, 5H), 8.01-8.04 (m, 2H).

Workup

  1. temperaturethe reaction mixture was heated
  2. temperatureunder reflux overnight
  3. customThe solution was evaporated
  4. dissolutionthe residue was dissolved in CH2Cl2 (30 ml)
  5. concentrationthe solution was concentrated in vacuo
  6. dissolutionThe residue was dissolved in CHCl3
  7. washwashed with sat. NaRCO3
  8. dry with materialdried over Na2SO4
  9. customevaporated
  10. customThe residue was purified by column chromatography on silica-gel with CHCl3 to CHCl3—MeOH (9:1

Sources & evidence

ORD record
ord-fd3820756701493f9b0cba66fd9c5177
Source dataset
uspto-grants-2004_06
Patent number
US06756378B2

Reaction notes

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