Bromine → HCID 69989621, compound

HRID 1358598Notes

Reaction equation

HRID 1358598 reaction equation
Cl.[CH3:2][O:3][C:4](=[O:25])[C@H:5]([CH2:7][C:8]1[CH:13]=[CH:12][C:11]([NH:14][C:15](=[O:24])[C:16]2[C:21]([Cl:22])=[CH:20][CH:19]=[CH:18][C:17]=2[Cl:23])=[CH:10][CH:9]=1)[NH2:6].[Br:26]Br>C(O)(=O)C.[Fe]>[ClH:22].[CH3:2][O:3][C:4](=[O:25])[C@H:5]([CH2:7][C:8]1[CH:9]=[CH:10][C:11]([NH:14][C:15](=[O:24])[C:16]2[C:17]([Cl:23])=[CH:18][CH:19]=[CH:20][C:21]=2[Cl:22])=[C:12]([Br:26])[CH:13]=1)[NH2:6]

Participants

5

Reactant 2

HCID 24408BromineHCID 23383932methyl (2S)-2-amino-3-{4-[(2,6-dichlorobenzoyl)amino]phenyl}propionate hydrochloride

Product 1

HCID 69989621HCID 69989621, compound

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolvent2×HCID 23925IronSolvent

Procedure

Reference Example 56 was prepared as follows: To a solution of 4-[(2,6-Dichlorobenzoyl)amino]-L-phenylalanine methyl ester hydrochloride salt, 37-B-1, (205.7 mg) in acetic acid(5 mL) was added an excess of bromine (5.55 g) in acetic acid (5 mL) and iron powder (416.2 mg). The reaction was stirred at ambient temperature for 3 hours. The reaction concentrated in vacuo and the remaining acetic acid removed as an azeotrope with toluene. The crude material was diluted with water, made basic with saturated sodium bicarbonate and extracted with AcOEt. The extract was purified by flash chromatography on silica gel eluting with methanol-methylene chloride. The purified material was dissolved in methanol saturated with hydrogen chloride and concentrated in vacuo and then crystallized from methanol with AcOEt to obtain 3-Bromo-4-[(2,6-dichlorobenzoyl)amino]-L-phenylalanine methyl ester hydrochloride salt (540.4 mg). Physical properties as follows: m.p. 200-205; 1H NMR (CD3OD) δ 7.76 (1H), 7.64 (1H), 7.46 (3H), 7.34 (1H), 4.38 (1H), 3.85 (3H), 3.30 (1H), 3.15 (1H); HRMS (FAB) Calcd for C17H15BRCL2N2O3+H1 444.9722, found 444.9724.

Workup

  1. customReference Example 56 was prepared
  2. concentrationThe reaction concentrated in vacuo
  3. customthe remaining acetic acid removed as an azeotrope with toluene
  4. additionThe crude material was diluted with water
  5. extractionextracted with AcOEt
  6. customThe extract was purified by flash chromatography on silica gel eluting with methanol-methylene chloride
  7. dissolutionThe purified material was dissolved in methanol saturated with hydrogen chloride
  8. concentrationconcentrated in vacuo
  9. customcrystallized from methanol with AcOEt

Sources & evidence

ORD record
ord-40f011327d9349cd802faa76fff5bad5
Source dataset
uspto-grants-2003_07
Patent number
US06596752B1

Reaction notes

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