Hydrochloric Acid → HCID 68529627, compound

HRID 2108662Notes

Reaction equation

HRID 2108662 reaction equation
FC(F)(F)S(O[C:7]1[CH:12]=[C:11]([CH3:13])[C:10]([CH2:14][C:15]2[CH:20]=[CH:19][C:18]([O:21][CH2:22][O:23][CH3:24])=[C:17]([CH2:25][C:26]3[CH:31]=[CH:30][C:29]([F:32])=[CH:28][CH:27]=3)[CH:16]=2)=[C:9]([CH3:33])[CH:8]=1)(=O)=O.[CH3:36][OH:37].C1C=CC(P(C2C=CC=CC=2)CCCP(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.Cl.CN([CH:71]=[O:72])C>CC([O-])=O.CC([O-])=O.[Pd+2]>[CH3:13][C:11]1[CH:12]=[C:7]([CH:8]=[C:9]([CH3:33])[C:10]=1[CH2:14][C:15]1[CH:20]=[CH:19][C:18]([O:21][CH2:22][O:23][CH3:24])=[C:17]([CH2:25][C:26]2[CH:27]=[CH:28][C:29]([F:32])=[CH:30][CH:31]=2)[CH:16]=1)[C:36]([O:72][CH3:71])=[O:37]

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 887MethanolHCID 6228DimethylformamideHCID 812191,3-Bis(diphenylphosphino)propaneHCID 86603469HCID 86603469, compound

Product 1

HCID 68529627HCID 68529627, compoundYield 100%

Reagents, catalysts & solvents 1

HCID 167845palladium(II) acetateCatalyst

Conditions

Temperature
90 °C

Procedure

To a solution of 3,5-dimethyl-4-[3′-(4-fluorobenzyl)-4′-methoxymethoxybenzyl]phenyl trifluoromethanesulfonate (5.8 g, 11.32 mmol) in DMF (80 mL) in a bomb apparatus was added MeOH (9.2 mL, 226.4 mmol), Pd(OAc)2 (0.25 g, 1.13 mmol), DPPP (0.47 g, 1.13 mmol) and TEA (3.2 mL, 22.64 mmol). 60 psi of CO was then infused and the reaction mixture was stirred at 90° C. for 16 h. The bomb was cooled to 0° C., vented, its content poured into cold 1 N HCl and extracted with EtOAc twice. The combined EtOAc extracts were washed with brine, dried over MgSO4, filtered and concentrated. The residue was purified by column chromatography on silica gel, eluting with ethyl acetate-hexanes (15:85) to afford methyl 3,5-dimethyl-4-[3′-(4-fluorobenzyl)-4′-methoxymethoxybenzyl]benzoate as a colorless oil (4.8 g, 100%): 1H NMR (200 MHz, DMSO-d6): δ 7.64 (s, 2H), 6.68-7.25 (m, 7H), 5.13 (s, 2H), 3.97 (s, 2H), 3.83 (s, 5H), 3.24 (s, 3H), 2.23 (s, 6H). TLC conditions: Uniplate silica gel, 250 microns; Mobile phase=ethyl acetate-hexanes (15:75); Rf=0.52.

Workup

  1. temperatureThe bomb was cooled to 0° C.
  2. extractionextracted with EtOAc twice
  3. washThe combined EtOAc extracts were washed with brine
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified by column chromatography on silica gel
  8. washeluting with ethyl acetate-hexanes (15:85)

Sources & evidence

ORD record
ord-7b15b35195e4462584f3f26f55c2c152
Source dataset
uspto-grants-2009_04
Patent number
US07514419B2

Reaction notes

Loading…