Water → (S)-2-(2-amino-4-iodo-benzoylamino)-3-(3,4-dichloro-phenyl)-propionic acid methyl ester

HRID 2265167Notes

Reaction equation

HRID 2265167 reaction equation
[I:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=O)=[C:4]([N+:11]([O-])=O)[CH:3]=1.Cl.[CH3:15][O:16][C:17](=[O:29])[CH:18]([NH2:28])[CH2:19][C:20]1[CH:25]=[CH:24][C:23]([Cl:26])=[C:22]([Cl:27])[CH:21]=1.O>O=S(Cl)Cl.CN(C1C=CN=CC=1)C>[CH3:15][O:16][C:17](=[O:29])[C@@H:18]([NH:28][C:6](=[O:8])[C:5]1[CH:9]=[CH:10][C:2]([I:1])=[CH:3][C:4]=1[NH2:11])[CH2:19][C:20]1[CH:25]=[CH:24][C:23]([Cl:26])=[C:22]([Cl:27])[CH:21]=1

Participants

6

Reactant 3

HCID 962WaterHCID 189198834-Iodo-2-nitrobenzoic acidHCID 68772138Methyl 2-amino-3-(3,4-dichlorophenyl)propanoate hydrochloride

Product 1

HCID 68770882(S)-2-(2-amino-4-iodo-benzoylamino)-3-(3,4-dichloro-phenyl)-propionic acid methyl esterYield 52.9%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 24386Thionyl ChlorideSolvent

Procedure

A solution of 4-iodo-2-nitrobenzoic acid (0.35 g, 1.20 mmol) dissolved in SOCl2 (5 mL) was heated at reflux for 2 h. The mixture was concentrated and the resulting liquid was dissolved in DMF (5 mL). DMAP (161 mg, 1.32 mmol) and 2-amino-3-(3,4-dichloro-phenyl)-propionic acid methyl ester hydrochloride (0.37 g, 1.32 mmol) were added and the solution was stirred overnight at rt. The mixture was poured into water and extracted with EtOAc (3×). The organic layers were combined, dried (MgSO4), and concentrated to provide the crude product as a yellow oil. The oil was purified by flash chromatography (hexanes/EtOAc) to provide the product as a colorless oil (50%, 313 mg). 1H NMR (400 MHz, CDCl3): 7.59 (d, J=8.1, 2H), 7.37 (d, J=8.2, 1H), 7.28 (d, J=2.0, 1H), 7.18 (d, J=8.0, 1H), 7.04 (dd, J=8.2, 2.0, 1H), 6.49 (d, J=7.4, 1H), 5.10-5.04 (m, 1H), 3.81 (s, 3H), 3.33-3.17 (m, 2H).

Workup

  1. temperaturewas heated
  2. temperatureat reflux for 2 h
  3. concentrationThe mixture was concentrated
  4. dissolutionthe resulting liquid was dissolved in DMF (5 mL)
  5. extractionextracted with EtOAc (3×)
  6. dry with materialdried (MgSO4)
  7. concentrationconcentrated
  8. customto provide the crude product as a yellow oil
  9. customThe oil was purified by flash chromatography (hexanes/EtOAc)

Sources & evidence

ORD record
ord-6ba34672ca65421ea76efa1b51219620
Source dataset
uspto-grants-2010_12
Patent number
US07855292B2

Reaction notes

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