Carbon tetrabromide → HCID 18761415, compound

HRID 431706Notes

Reaction equation

HRID 431706 reaction equation
C([O:8][C:9]1[CH:14]=[CH:13][C:12]([CH2:15][CH2:16][Br:17])=[C:11]([N+:18]([O-])=O)[CH:10]=1)C1C=CC=CC=1.C(OC1C=CC(CCO)=C([N+]([O-])=O)C=1)C1C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(Br)(Br)(Br)Br.C([O:72][C:73]1[CH:78]=[CH:77][C:76]([CH2:79][CH2:80][Cl:81])=[C:75]([N+:82]([O-])=O)[CH:74]=1)C1C=CC=CC=1>C(#N)C.C1COCC1.[Pd]>[NH2:82][C:75]1[CH:74]=[C:73]([OH:72])[CH:78]=[CH:77][C:76]=1[CH2:79][CH2:80][Cl:81].[NH2:18][C:11]1[CH:10]=[C:9]([OH:8])[CH:14]=[CH:13][C:12]=1[CH2:15][CH2:16][Br:17]

Participants

10

Reactant 5

HCID 11205Carbon tetrabromideHCID 11776TriphenylphosphineHCID 18761406HCID 18761406, compound2×HCID 18761413HCID 18761413, compoundHCID 18761444HCID 18761444, compound

Product 2

HCID 18761415HCID 18761415, compoundHCID 18761430HCID 18761430, compound

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 6342AcetonitrileSolventHCID 8028TetrahydrofuranSolvent

Procedure

The synthetic approach for the proposed achiral seco-CI compounds starts from the reaction of the readily available diethyl 2-(4-benzyloxy-2-nitrophenyl)malonate (4c). Treatment of diethyl 2-(4-benzyloxy-2-nitrophenyl)malonate with NaOH in ethanol (25-80° C.), preferably refluxing, followed by acidification and mild heating (25-100° C.), preferably refluxing, the solution gave the desired 4-benzyloxy-2-nitrophenylacetic acid in 95% yield. Selective reduction of the carboxylic acid with borane at 0-50° C., preferably at room temperature, in THF produced 2-(4-benzyloxy-2-nitrophenyl)ethanol in 95% yield. The alcohol was then chlorinated at 0-50° C., preferably at room temperature, with triphenylphosphine and carbon tetrachloride in CH2Cl2 to give 2-(4-benzyloxy-2-nitrophenyl)ethyl chloride in 97% yield. The 2-(4-benzyloxy-2-nitrophenyl)ethyl bromide was obtained in 92% yield after reacting 2-(4-benzyloxy-2-nitrophenyl)ethanol with triphenylphosphine and carbon tetrabromide in acetonitrile. Catalytic reduction of 2-(4-benzyloxy-2-nitrophenyl)ethyl chloride and 2-(4-benzyloxy-2-nitrophenyl)ethyl bromide at atmospheric pressure, and at 0-50° C., preferably at room temperature, using 10% Pd/C in THF afforded 2-(2-amino-4-hydroxyphenyl)ethyl chloride and 2-(2-amino-4-hydroxyphenyl)ethyl bromide, respectively. 2-(2-Amino-4-hydroxyphenyl)ethyl bromide was directly coupled at 0-50° C., preferably at room temperature, with 5-(benzofuran-2-carboxamido)indole-2-carboxylic acid in the presence of EDCI [1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride] and DMF to give compound 4-(2-bromoethyl)-3-[5-(5-benzofuran-2-carboxamido)indole-2-carboxamido]phenol in a low 2% yield for the two steps after purification by silica gel column chromatography. Similarly, coupling of 2-(2-amino-4-hydroxyphenyl)ethyl chloride with 5-(benzofuran-2-carboxamido)indole-2-carboxylic acid in the presence of EDCI gave 4-(2-chloroethyl)-3-[5-(5-benzofuran-2-carboxamido)indole-2-carboxamido]phenol in 28% yield for the two steps following column chromatography.

Workup

  1. customat 0-50° C.
  2. custompreferably at room temperature

Sources & evidence

ORD record
ord-ad6222215bcb4f62bd9334f4dec02d7d
Source dataset
uspto-grants-2003_12
Patent number
US06660742B2

Reaction notes

Loading…