Benzene, 1-(bromomethyl)-3-nitro- → Ethyl 2-amino-3-(3-nitrophenyl)propanoate

HRID 279072Notes

Reaction equation

HRID 279072 reaction equation
[Li+].CC([N-]C(C)C)C.C1(C(C2C=CC=CC=2)=[N:16][CH2:17][C:18]([O:20][CH2:21][CH3:22])=[O:19])C=CC=CC=1.[N+:29]([C:32]1[CH:33]=[C:34]([CH:37]=[CH:38][CH:39]=1)[CH2:35]Br)([O-:31])=[O:30]>C1COCC1>[CH2:21]([O:20][C:18](=[O:19])[CH:17]([CH2:35][C:34]1[CH:37]=[CH:38][CH:39]=[C:32]([N+:29]([O-:31])=[O:30])[CH:33]=1)[NH2:16])[CH3:22]

Participants

5

Reactant 3

HCID 77568Benzene, 1-(bromomethyl)-3-nitro-HCID 319508Ethyl 2-(diphenylmethyleneamino)acetateHCID 2724682Lithium diisopropylamide

Product 1

HCID 5040514Ethyl 2-amino-3-(3-nitrophenyl)propanoateYield 96%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

LDA (2M in heptane/THF/ethyl benzene, 25.45 ml, 50.9 mmol) was added dropwise to a solution of ethyl N-(diphenylmethylene)glycinate (13 g, 48.5 mmol) in THF (200 ml) at −78°. After 40 min a solution of 3-nitrobenzyl bromide (10 g, 46.3 mmol) in THF (40 ml) was added dropwise. The mixture was stirred for 2 h and then partitioned between EtOAc (100 ml) and water (100 ml). The aqueous layer was separated and extracted with EtOAc (2×50 ml) and the combined organics dried (Na2SO4) and evaporated in vacuo. The residue was then dissolved in ethanol (200 ml) and hydrochloric acid (1M, 50 ml) was added and the mixture stirred for 0.25 h. The volatiles were then removed in vacuo and the residue purified by chromatography (SiO2, Et2O) to give the title compound as an orange oil (10.0 g, 96%). δH (CDCl3) 8.09-8.06 (2H, m, Ar), 7.56-7.53 (1H, m, ArH), 7.48-7.43 (1H, m, ArH), 4.15 (2H, q, J 7.2, OCH2CH3), 3.71 (1H, dd, J 7.8, 5.5 Hz, CHCH2), 3.14 (1H, dd, J 13.7, 5.5 Hz, CHCHAHB)2.95 (1H, dd, J 13.7, 7.8 Hz, CHCHAHB), 1.51 (2H, br s, NH2) and 1.23 (3H, t, J 7.2, OCH2CH3); m/z (ESI, 60V) 239 (M++1).

Workup

  1. custompartitioned between EtOAc (100 ml) and water (100 ml)
  2. customThe aqueous layer was separated
  3. extractionextracted with EtOAc (2×50 ml)
  4. dry with materialthe combined organics dried (Na2SO4)
  5. customevaporated in vacuo
  6. dissolutionThe residue was then dissolved in ethanol (200 ml)
  7. additionhydrochloric acid (1M, 50 ml) was added
  8. stirringthe mixture stirred for 0.25 h
  9. customThe volatiles were then removed in vacuo
  10. customthe residue purified by chromatography (SiO2, Et2O)

Sources & evidence

ORD record
ord-553b06e885764263884f82154fd80009
Source dataset
uspto-grants-2002_03
Patent number
US06362204B1

Reaction notes

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