Hydrochloric Acid → HCID 66642921, compound

HRID 1170996Notes

Reaction equation

HRID 1170996 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][CH:29]=[CH:28][CH:27]=3)[CH:16]=2)=[C:9]([CH3:32])[CH:8]=1)(=O)=O.[CH3:35][OH:36].C1(P(C(P(C2C=CC=CC=2)C2C=CC=CC=2)(C)C)C2C=CC=CC=2)C=CC=CC=1.Cl.CN([CH:70]=[O:71])C>CC([O-])=O.CC([O-])=O.[Pd+2]>[CH2:25]([C:17]1[CH:16]=[C:15]([CH:20]=[CH:19][C:18]=1[O:21][CH2:22][O:23][CH3:24])[CH2:14][C:10]1[C:9]([CH3:32])=[CH:8][C:7]([C:35]([O:71][CH3:70])=[O:36])=[CH:12][C:11]=1[CH3:13])[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 887MethanolHCID 6228DimethylformamideHCID 12091099Phosphine, (1-methylethylidene)bis[diphenyl-HCID 86603459HCID 86603459, compound

Product 1

HCID 66642921HCID 66642921, compoundYield 88%

Reagents, catalysts & solvents 1

HCID 167845palladium(II) acetateCatalyst

Conditions

Temperature
90 °C

Procedure

To a solution of 4-(3′-benzyl-4′-methoxymethoxy-benzyl)-3,5-dimethyl-phenyl trifluoromethanesulfonate (0.5 g, 1 mmol) in DMF (8 mL) in a bomb apparatus was added MeOH (0.82 mL, 20 mmol), Pd(OAc)2 (23 mg, 0.1 mmol), bis-(diphenyphosphino)propane (42 mg, 0.1 mmol) and TEA (0.28 mL, 2 mmol). 60 psi of CO was then infused and the reaction mixture was stirred at 90° C. for 16 h. The cooled bomb was vented and the reaction mixture was poured into cold 1N HCl, extracted with EtOAc twice, the combined EtOAc were washed with brine, dried over MgSO4, filtrated and concentrated. The residue was purified by column chromatography on silica gel, eluting with ethyl acetate-hexanes (15:75) to afford methyl 4-(3′-benzyl-4′-methoxymethoxy-benzyl)-3,5-dimethyl-benzoate as a yellow oil (360 mg, 88%): 1H NMR (300 MHz, DMSO-d6): δ 7.66 (s, 2 H), 7.16 (m, 5 H), 6.90 (m, 2 H), 6.71 (m, 1 H), 5.15 (s, 2 H), 3.98 (s, 2 H), 3.87 (s, 2 H), 3.85 (s, 3 H), 3.26 (s, 3 H), 2.25 (s, 6 H). TLC conditions: Uniplate silica gel, 250 microns; Mobile phase=ethyl acetate-hexanes (15:75); Rf=0.50.

Workup

  1. extractionextracted with EtOAc twice
  2. washthe combined EtOAc were washed with brine
  3. dry with materialdried over MgSO4
  4. filtrationfiltrated
  5. concentrationconcentrated
  6. customThe residue was purified by column chromatography on silica gel
  7. washeluting with ethyl acetate-hexanes (15:75)

Sources & evidence

ORD record
ord-3aa7e6967bd54b438c61dcb5587292ef
Source dataset
uspto-grants-2010_11
Patent number
US07829552B2

Reaction notes

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