(3-Bromopropyl)benzene → (2R)-3-benzyloxy-2-aminopropanoic acid methyl ester

HRID 2269528Notes

Reaction equation

HRID 2269528 reaction equation
[O-][CH2:2]C.[Na+].[Na].C(C(CC)C([NH:11][CH:12]([C:16]([O-:18])=[O:17])[C:13]([O-:15])=O)=O)C.BrCC[CH2:24][C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1>C(O)C>[CH3:2][O:18][C:16](=[O:17])[C@@H:12]([CH2:13][O:15][CH2:24][C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1)[NH2:11]

Participants

6

Reactant 4

HCID 12503(3-Bromopropyl)benzeneHCID 2723922Sodium ethoxide2×HCID 5360545SodiumHCID 21751412Diethylacetamidomalonate

Product 1

HCID 13635389(2R)-3-benzyloxy-2-aminopropanoic acid methyl esterYield 98%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent2×

Procedure

A solution of sodium ethoxide was generated by the addition of sodium metal (52.89 grams, 2.3007 mol) over 3 hours to ethanol (1500 mL). To the sodium ethoxide solution at ambient temperature was added a solution of diethylacetamidomalonate (499.75 grams, 2.3007 mol) dissolved in ethanol (225 mL). The reaction mixture was stirred for 1.5 hours at ambient temperature. 1-bromo-3-phenylpropane (458.07 grams, 2.3007 mol) was added over 15 minutes and the reaction mixture was refluxed until complete as determined by hplc (16 hours). The reaction mixture was concentrated to dryness and the residue partitioned between ethyl acetate (1×1500 mL and 2×500 mL) and water (1500 mL). The ethyl acetate layers were combined, washed with saturated sodium chloride solution (4×500 mL), dried using sodium sulfate, and concentrated to give 752.1 grams (98%) of the desired compound as a light yellow solid. A 1.0 gram sample was recrystallized from hexane:ethyl acetate (19:1, v:v) to give a mp 84-86° C. 1H nmr (CDCl3): δ1.18-1.23 (t, 6H), 1.37-1.50 (m, 2H), 2.02 (s, 3H), 2.34-2.41 (m, 2H), 2.58-2.62 (t, 2H), 4.16-4.24 (q, 4H), 6.76 (s, broad, 1H), 7.11-7.28 (m, 5H). 13C nmr (CDCl3): δ13.95, 23.03, 25.67, 31.85, 35.45, 62.46, 66.49, 125.40, 125.90, 128.27, 128.35, 141.77, 168.11, 168.94. MS (FIA) m/z 336.3 ([M+H]+). IR (KBr, cm−1) 1645.98 (amide), 1744.76 (C=O). Anal. Calcd. for C18H25NO5: C, 64.46; H, 7.51; N, 4.17. Found: C, 64.60; H, 7.37; N, 4.39.

Workup

  1. temperaturethe reaction mixture was refluxed until complete
  2. customas determined by hplc (16 hours)
  3. concentrationThe reaction mixture was concentrated to dryness
  4. customthe residue partitioned between ethyl acetate (1×1500 mL and 2×500 mL) and water (1500 mL)
  5. washwashed with saturated sodium chloride solution (4×500 mL)
  6. customdried
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-f5e73a5f6d9d488aad3c1508ac2c062b
Source dataset
uspto-grants-2001_12
Patent number
US06329342B1

Reaction notes

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