(+)-Benzylphenethylamine → 3-[Benzyl-(1(R)-phenylethyl)-amino]-3-(2-fluoro-biphenyl-4-yl)-propionic acid ethyl ester

HRID 850615Notes

Reaction equation

HRID 850615 reaction equation
[CH2:1]([NH:8][C@H:9]([CH3:16])[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C([Li])CCC.[CH2:22]([O:24][C:25](=[O:41])[CH:26]=[CH:27][C:28]1[CH:33]=[CH:32][C:31]([C:34]2[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=2)=[C:30]([F:40])[CH:29]=1)[CH3:23]>C1COCC1>[CH2:22]([O:24][C:25](=[O:41])[CH2:26][CH:27]([N:8]([CH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1)[C@@H:9]([C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1)[CH3:16])[C:28]1[CH:33]=[CH:32][C:31]([C:34]2[CH:35]=[CH:36][CH:37]=[CH:38][CH:39]=2)=[C:30]([F:40])[CH:29]=1)[CH3:23]

Participants

5

Reactant 3

HCID 1268086(+)-BenzylphenethylamineHCID 542096623-(2-Fluoro-biphenyl-4-yl)-acrylic acid ethyl esterHCID 178418339Butyllithium

Product 1

HCID 697797503-[Benzyl-(1(R)-phenylethyl)-amino]-3-(2-fluoro-biphenyl-4-yl)-propionic acid ethyl ester

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

A cooled (0° C.) solution of (R)-(+)-N-benzyl-α-methylbenzylamine (8.9 mL, 42.6 mmol) in THF (100 mL) was treated with n-butyllithium (26.6 mL of a 1.6 M soln in hexanes; 42.6 mmol). After stirring for 10 min, the purple solution was cooled to -78° C. and treated with a solution of ester 12-2 (5.76 g, 21.3 mmol) in THF (10 mL). After stirring for 20 min, the solution was quenched with satd aq NH4Cl soln (5 mL), and the cold bath removed. The reaction mixture was diluted with Et2O (100 mL), and washed with 10% aq citric acid (50 mL), satd aq NaHCO3 (50 mL), 5% aq acetic acid (30 mL), 10% aq K2CO3 (50 mL), and brine (50 mL). The solution was dried over MgSO4, filtered and concentrated. The residue was purified by flash chromatography (90:10 hexanes/EtOAc) to give adduct 12-3.

Workup

  1. stirringAfter stirring for 20 min
  2. customthe solution was quenched with satd aq NH4Cl soln (5 mL)
  3. customthe cold bath removed
  4. additionThe reaction mixture was diluted with Et2O (100 mL)
  5. washwashed with 10% aq citric acid (50 mL)
  6. dry with materialThe solution was dried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe residue was purified by flash chromatography (90:10 hexanes/EtOAc)

Sources & evidence

ORD record
ord-d7cfc4be38fb4202adadafb970cc208b
Source dataset
uspto-grants-2000_01
Patent number
US06017926

Reaction notes

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