Dicyclohexylcarbodiimide → HCID 86713102, compound

HRID 1399423Notes

Reaction equation

HRID 1399423 reaction equation
[I:1][C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][C:10]=1[N+:11]([O-:13])=[O:12])[C:5]([OH:7])=O.[NH2:14][CH2:15][C:16]([O:18][CH2:19][C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1)=[O:17].C1CCC(N=C=NC2CCCCC2)CC1>CN(C1C=CN=CC=1)C>[I:1][C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][C:10]=1[N+:11]([O-:13])=[O:12])[C:5]([NH:14][CH2:15][C:16]([O:18][CH2:19][C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1)=[O:17])=[O:7]

Participants

5

Reactant 3

HCID 10868DicyclohexylcarbodiimideHCID 409140Benzyl glycinateHCID 53420329HCID 53420329, compound

Product 1

HCID 86713102HCID 86713102, compound

Reagents, catalysts & solvents 1

HCID 142844-(Dimethylamino)pyridineCatalyst

Procedure

As shown in scheme F, condensation of 3-iodo-4-nitrobenzoic acid with benzyl glycinate in presence of DCC and catalytic amount of DMAP gave benzyl 2-(3-iodo-4-nitrobenzamido)acetate, which on oxidation using oxidizing agents such as acetic anhydride-hydrogen peroxide gave benzyl 2-(3-iodyl-4-nitrobenzamido)acetate (intermediate 7). The intermediate 7 is treated either with K18F or K19F in the presence of kryptofix[2.2.2] or 18-crown-6 to yield benzyl 2-(3-fluoro-4-nitrobenzamido)acetate, which on reduction with hydrogen gas or hydrogen source in the presence of Pd/C gave 2-(4-amino-3-fluorobenzamido)acetic acid (compound 6). Reaction of 3-iodo-4-nitrobenzoic acid with thionyl chloride gave 3-iodo-4-nitrobenzoyl chloride, which on further treatment with 2,2,2-trichloroethyl glycinate in the presence of triethylamine gave 2,2,2-trichloroethyl 2-(3-iodo-4-nitrobenzamido)acetate. Oxidation of 2,2,2-trichloroethyl 2-(3-iodo-4-nitrobenzamido)acetate with acetic anhydride-hydrogen peroxide gave 2,2,2-trichloroethyl 2-(3-iodyl-4-nitrobenzamido)acetate (intermediate 8). Reaction of intermediate 8 either with K18F or K19F gave 2,2,2-trichloroethyl 2-(3-fluoro-4-nitrobenzamido)acetate, which on reduction with zinc dust gave compound 6. In an analogous manner, treatment of 3-iodo-4-nitrobenzoyl chloride with glycine in presence of sodium carbonate gave 2-(3-iodo-4-nitrobenzamido)acetic acid, which on oxidation with acetic anhydride-hydrogen peroxide and followed by treatment with KOH gave potassium 2-(3-iodyl-4-nitrobenzamido)acetate (intermediate 9). The intermediate 9 is treated either with K18F or K19F to yield 2-(3-fluoro-4-nitrobenzamido)acetic acid, which on reduction with iron powder in presence of acetic acid gave compound 6. Reduction of 2-(3-fluoro-4-nitrobenzamido)acetic acid with iron powder in the presence of acetic anhydride-acetic acid gave 2-(4-acetamido-3-fluorobenzamido)acetic acid (compound 7).

Sources & evidence

ORD record
ord-ad313e84727f4a9e9e39d2f49ded1c39
Source dataset
uspto-grants-2014_12
Patent number
US08906344B2

Reaction notes

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