Hydrochloric Acid → HCID 66799669, compound

HRID 404959Notes

Reaction equation

HRID 404959 reaction equation
[CH:1]1([N:6]2[CH2:14][C:13]3[C:8](=[CH:9][CH:10]=[C:11]([O:15][CH2:16][C:17]4[CH:18]=[C:19](B(O)O)[CH:20]=[CH:21][CH:22]=4)[CH:12]=3)[C:7]2=[O:26])[CH2:5][CH2:4][CH2:3][CH2:2]1.I[C:28]1[CH:29]=[C:30]([CH:34]=[CH:35][C:36]=1[O:37][CH3:38])[C:31]([OH:33])=[O:32].C([O-])([O-])=O.[K+].[K+].Cl>C1(C)C=CC=CC=1.CO.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[CH:1]1([N:6]2[CH2:14][C:13]3[C:8](=[CH:9][CH:10]=[C:11]([O:15][CH2:16][C:17]4[CH:18]=[C:19]([C:35]5[C:36]([O:37][CH3:38])=[CH:28][CH:29]=[C:30]([C:31]([OH:33])=[O:32])[CH:34]=5)[CH:20]=[CH:21][CH:22]=4)[CH:12]=3)[C:7]2=[O:26])[CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 11430Potassium CarbonateHCID 6241583-Iodo-4-methoxybenzoic acidHCID 66799705HCID 66799705, compound

Product 1

HCID 66799669HCID 66799669, compoundYield 13.1%

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 21867641Toluene methanolSolvent

Conditions

Temperature
80 °C

Procedure

3-((2-Cyclopentyl-1-oxoisoindolin-5-yloxy)methyl)phenylboronic acid (30 mg, 0.08 mmol), 3-iodo-4-methoxybenzoic acid (19.7 mg, 0.07 mmol), K2CO3 (29 mg, 0.21 mmol) and PdCl2(PPh3)2 (6.2 mg, 0.009 mmol) were dissolved in a mixture of toluene-MeOH (1.1 mL:0.1 mL) and heated at 80° C. for 1.5 hours. The mixture was filtered through celite washed with water and solvent was removed was evaporated in vacuo. The resulted crude material was acidified with 2 M HCl, extracted into EtOAc and dried over anhyd. Na2SO4, evaporated solvent in vacuo to obtain the crude acid which was purified using automated prep-HPLC to yield the desired compound 4.2 mg, 13%) as a white solid. 1H NMR (400 MHz, DMSO-d6): δ 7.93 (d, J=8.2 Hz, 1H), 7.82 (s, 1H), 7.55-7.42 (m, 5H), 7.21-7.18 (m, 2H), 7.10 (dd, J=8.7 Hz, J=2.3 Hz, 1H), 5.23 (s, 2H), 4.54-4.46 (m, 1H), 4.37 (s, 2H), 3.84 (s, 3H), 1.85-1.80 (m, 2H), 1.71-1.56 (m, 6H). LRMS calcd. for C28H27NO5 [M+H]+ 458 found: 458.

Workup

  1. filtrationThe mixture was filtered through celite
  2. washwashed with water and solvent
  3. customwas removed
  4. customwas evaporated in vacuo
  5. customThe resulted crude material
  6. extractionextracted into EtOAc
  7. customdried over anhyd
  8. customNa2SO4, evaporated solvent in vacuo
  9. customto obtain the crude acid which
  10. customwas purified

Sources & evidence

ORD record
ord-b338db00efb548f493a452d73ebab28e
Source dataset
uspto-grants-2014_06
Patent number
US08748632B2

Reaction notes

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