Methanol → 2-(2-Benzyloxypyridin-3-yl)-4-tert-butyl-5-methoxybenzoic acid methyl ester

HRID 1517534Notes

Reaction equation

HRID 1517534 reaction equation
[CH3:1][O:2][C:3](=[O:17])[C:4]1[CH:9]=[C:8]([O:10][CH3:11])[C:7]([C:12]([CH3:15])([CH3:14])[CH3:13])=[CH:6][C:5]=1Br.[CH2:18]([O:25][C:26]1[C:31](B2OC(C)(C)C(C)(C)O2)=[CH:30][CH:29]=[CH:28][N:27]=1)[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1.C([O-])([O-])=O.[Na+].[Na+].CO>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C(Cl)Cl>[CH3:1][O:2][C:3](=[O:17])[C:4]1[CH:9]=[C:8]([O:10][CH3:11])[C:7]([C:12]([CH3:15])([CH3:14])[CH3:13])=[CH:6][C:5]=1[C:31]1[C:26]([O:25][CH2:18][C:19]2[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=2)=[N:27][CH:28]=[CH:29][CH:30]=1

Participants

7

Reactant 4

HCID 887MethanolHCID 10340Sodium CarbonateHCID 447551622-(Benzyloxy)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridineHCID 67379187HCID 67379187, compound

Product 1

HCID 673789942-(2-Benzyloxypyridin-3-yl)-4-tert-butyl-5-methoxybenzoic acid methyl esterYield 80%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 6344DichloromethaneSolvent

Procedure

step 2—A microwave vial was charged with 64 (903 mg, 3.00 mmol), 2-benzyloxy-3-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)pyridine (1.12 g, 3.60 mmol), Pd(PPh3)4 (173 mg, 0.15 mmol), Na2CO3 (950 mg, 9.00 mmol), MeOH (10 mL) and DCM (3 mL). The vial was sealed and irradiated at 115° C. for 30 min in microwave synthesizer. The reaction was quenched with H2O and extracted with DCM. The combined organics were dried (MgSO4) and concentrated under reduced pressure. The residue was purified by SiO2 chromatography eluting with a EtOAc/hexane gradient (10% to 20% EtOAc) to afford 964 mg (80%) of 2-(2-benzyloxypyridin-3-yl)-4-tert-butyl-5-methoxybenzoic acid methyl ester (66) as a light yellow solid.

Workup

  1. customThe vial was sealed
  2. customirradiated at 115° C. for 30 min in microwave synthesizer
  3. customThe reaction was quenched with H2O
  4. extractionextracted with DCM
  5. dry with materialThe combined organics were dried (MgSO4)
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by SiO2 chromatography
  8. washeluting with a EtOAc/hexane gradient (10% to 20% EtOAc)

Sources & evidence

ORD record
ord-df5b31e47f7a4c8bb0993dba7c880a3a
Source dataset
uspto-grants-2012_07
Patent number
US08232271B2

Reaction notes

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