Dimethylformamide → Methyl 4-hydroxy-3-iodobenzoate

HRID 1697821Notes

Reaction equation

CC(OC(N[C@@H:9](CC1C=CC(C2N=C(C(N(C)OC)=O)N(C)C=2)=CC=1)[CH2:10][CH2:11][C:12]([O:14][C:15](C)(C)C)=[O:13])=O)(C)C.[I:38][CH:39]([CH3:41])[CH3:40].CCN(C(C)C)C(C)C.CN(C=[O:55])C>>[OH:55][C:40]1[CH:9]=[CH:10][C:11]([C:12]([O:14][CH3:15])=[O:13])=[CH:41][C:39]=1[I:38]

Participants

Reactant 4

HCID 6228Dimethylformamide

HCID 6362Isopropyl iodide

HCID 81531Diisopropylethylamine

HCID 866047661,1-dimethylethyl (4R)-4-({[(1,1-dimethylethyl)oxy]carbonyl)amino)-5-[4-(1-methyl-2-{[methyl(methyloxy)amino]carbonyl}-1H-imidazol-4-yl)phenyl]pentanoate

Product 1

HCID 11346465Methyl 4-hydroxy-3-iodobenzoateYield 20%

Conditions

Temperature: 80 °C

Procedure

To a solution of compound 1 (200 mg, 1.077 mmol) and 2-iodopropane (322 uL, 3.23 mmol) in DMF (10 mL) was added DIEA (750 uL, 4.31 mmol). The reaction mixture was heated to 80° C. and stirred overnight. When complete by LC/MS, the reaction was cooled to room temperature, quenched with HCl (0.5 N, 30 mL) and extracted with ethyl acetate (50 mL×3). The combined organic layers were dried over sodium sulfate, concentrated and dried under high vacuum. The resulting residue was purified by reverse phase chromatography using a mixture of acetonitrile and water to give compound 2 (50 mg, 20%).

Workup

temperatureWhen complete by LC/MS, the reaction was cooled to room temperature
customquenched with HCl (0.5 N, 30 mL)
extractionextracted with ethyl acetate (50 mL×3)
dry with materialThe combined organic layers were dried over sodium sulfate
concentrationconcentrated
customdried under high vacuum
customThe resulting residue was purified by reverse phase chromatography
additiona mixture of acetonitrile and water

Sources & evidence

ORD record: ord-80f0f737e67947b4b5b81a32a62dcec3
Source dataset: uspto-grants-2012_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08163919B2

Reaction notes

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