Water → (S)-ethyl 2-((3-bromo-2-nitrophenyl)amino)-propanoate

HRID 1055950Notes

Reaction equation

HRID 1055950 reaction equation
CCN(C(C)C)C(C)C.Cl.[CH2:11]([O:13][C:14](=[O:18])[C@H:15]([CH3:17])[NH2:16])[CH3:12].[Br:19][C:20]1[CH:25]=[CH:24][CH:23]=[C:22](F)[C:21]=1[N+:27]([O-:29])=[O:28].O>CN(C)C(=O)C.[NH4+].[Cl-]>[Br:19][C:20]1[C:21]([N+:27]([O-:29])=[O:28])=[C:22]([NH:16][C@@H:15]([CH3:17])[C:14]([O:13][CH2:11][CH3:12])=[O:18])[CH:23]=[CH:24][CH:25]=1

Participants

7

Reactant 4

HCID 962WaterHCID 81531DiisopropylethylamineHCID 2724356L-Alanine, ethyl ester, hydrochloride (1:1)HCID 27831521-Bromo-3-fluoro-2-nitrobenzene

Product 1

HCID 118521547(S)-ethyl 2-((3-bromo-2-nitrophenyl)amino)-propanoateYield 102.7%

Reagents, catalysts & solvents 2

HCID 25517Ammonium ChlorideSolventHCID 31374DimethylacetamideSolvent

Procedure

DIPEA (45.1 mL, 259 mmol) was added to a stirred solution of L-alanine ethyl ester hydrochloride (Aldrich; 34.1 g, 222 mmol) and 1-bromo-3-fluoro-2-nitrobenzene (126a; Ark Pharm, Inc., Libertyville, Ill.; 16.29 g, 74.0 mmol) in N,N-dimethylacetamide (15 mL) and the resulting yellow solution was stirred at RT for 15 min. A water-cooled reflux condenser was attached to the flask, and the resulting mixture was heated at 80° C. for 18 h. The reaction was cooled to RT, diluted with saturated aq. NH4Cl (100 mL), and extracted with EtOAc (4×75 mL). The combined organic extracts were dried over Na2SO4, filtered, and concentrated in vacuo to provide (S)-ethyl 2-((3-bromo-2-nitrophenyl)amino)propanoate (126b; 24.1 g) as a brown residue (contains 10% starting material by LCMS and 1H NMR), which was used directly in the subsequent step: 1H NMR (400 MHz, CDCl3) δ ppm 7.13 (1H, t, J=8.2 Hz), 7.00 (1H, d, J=8.0 Hz), 6.64 (1H, d, J=8.4 Hz), 5.89 (1H, d, J=6.8 Hz), 4.22 (2H, m, J=7.0, 7.0, 7.0 Hz), 4.14 (1H, quin, J=7.1 Hz), 1.51 (3H, d, J=7.0 Hz), 1.27 (3H, t, J=7.1 Hz). m/z (ESI, +ve) 317.0 (M+H)+.

Workup

  1. temperaturereflux condenser
  2. temperaturethe resulting mixture was heated at 80° C. for 18 h
  3. temperatureThe reaction was cooled to RT
  4. extractionextracted with EtOAc (4×75 mL)
  5. dry with materialThe combined organic extracts were dried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-e17e968129464b55ba237dedbfa9881e
Source dataset
uspto-grants-2016_07
Patent number
US09394297B2

Reaction notes

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