Water → 5-Dibenzylamino-4-fluoro-isophthalic acid 3-ethyl ester

HRID 1436718Notes

Reaction equation

[CH2:1]([O:3][C:4](=[O:28])[C:5]1[CH:10]=[C:9](Br)[CH:8]=[C:7]([N:12]([CH2:20][C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[CH2:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[C:6]=1[F:27])[CH3:2].C1(P(C2C=CC=CC=2)CCCCP(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(N(CC)CC)C.[OH2:66].[C]=O.[C:69]([OH:73])(C)(C)C>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.CS(C)=O>[CH2:1]([O:3][C:4](=[O:28])[C:5]1[CH:10]=[C:9]([CH:8]=[C:7]([N:12]([CH2:20][C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[CH2:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[C:6]=1[F:27])[C:69]([OH:73])=[O:66])[CH3:2]

Participants

Conditions

Temperature: 80 °C

Procedure

Combine 5-bromo-3-dibenzylamino-2-fluorobenzoic acid ethyl ester (4.74 g, 10.7 mmol), palladium (II) acetate (0.72 g, 3.20 mmol), 1,4-bis(diphenylphosphino)butane (2.84 g, 6.66 mmol), triethylamine (7.90 mL, 56.7 mmol), DMSO (150 mL), tert-butyl alcohol (100 mL), and water (0.50 mL, 27.8 mmol). Place mixture in a container pressurized to 100 psi with carbon monoxide and heat at 80° C. for 24 h. Filter the reaction mixture over a pad of filtering agent. Pour the filtrate into water (500 mL), acidify with 5 N HCl and extract (2×500 mL) with ethyl acetate. Dry (magnesium sulfate), concenetrate and purify (silica gel chromatography, eluting with 4:96 methanol:dichloromethane) to give the title compound as a solid (2.40 g, 55%).

Workup

filtrationFilter the reaction mixture over a pad
filtrationof filtering agent
additionPour the filtrate into water (500 mL)
extractionextract (2×500 mL) with ethyl acetate
dry with materialDry (magnesium sulfate), concenetrate
custompurify
wash(silica gel chromatography, eluting with 4:96 methanol:dichloromethane)

Sources & evidence

ORD record: ord-ba2de34b81224fcda011393b2163de6c
Source dataset: uspto-grants-2009_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07618978B2

Reaction notes

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