Nitrogen → Methyl 4-(cyclopropoxy)-3-[(4-methoxyphenyl)methylsulfanyl]benzoate

HRID 713154Notes

Reaction equation

HRID 713154 reaction equation
Br[C:2]1[CH:3]=[C:4]([CH:9]=[CH:10][C:11]=1[O:12][CH:13]1[CH2:15][CH2:14]1)[C:5]([O:7][CH3:8])=[O:6].[CH3:16][O:17][C:18]1[CH:23]=[CH:22][C:21]([CH2:24][SH:25])=[CH:20][CH:19]=1.CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.CCN(C(C)C)C(C)C.N#N>C1(C)C=CC=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH:13]1([O:12][C:11]2[CH:10]=[CH:9][C:4]([C:5]([O:7][CH3:8])=[O:6])=[CH:3][C:2]=2[S:25][CH2:24][C:21]2[CH:22]=[CH:23][C:18]([O:17][CH3:16])=[CH:19][CH:20]=2)[CH2:15][CH2:14]1

Participants

8

Reactant 5

HCID 947NitrogenHCID 804074-Methoxy-alpha-toluenethiolHCID 81531DiisopropylethylamineHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 117924638Methyl 3-bromo-4-cyclopropoxybenzoate

Product 1

HCID 118222046Methyl 4-(cyclopropoxy)-3-[(4-methoxyphenyl)methylsulfanyl]benzoateYield 89.34%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Procedure

To a solution of methyl 3-bromo-4-(cyclopropoxy)benzoate (530.00 mg, 1.95 mmol, 1.00 eq) and (4-methoxyphenyl)methanethiol (451.12 mg, 2.93 mmol, 1.50 eq) in toluene (10.00 mL) were added Pd2(dba)3 (89.28 mg, 97.50 umol, 0.05 eq), Xantphos (112.83 mg, 195.00 umol, 0.10 eq) and DIPEA (504.04 mg, 3.90 mmol, 2.00 eq) under N2 protection. Then the mixture was stirred at 100° C. for 16 hr N2 protection. TLC detected the reaction was complete, the solvent was evaporated, the residue was washed with water, the aqueous layer was extracted with EA, the combined organic layer was dried over Na2SO4, concentrated, the residue was purified by silica gel chromatography (PE:EA=5:1) to afford product methyl 4-(cyclopropoxy)-3-[(4-methoxyphenyl)methylsulfanyl]benzoate (600.00 mg, 1.74 mmol, 89.34% yield) as white solid. LCMS: 345 [M+1].

Workup

  1. customthe solvent was evaporated
  2. washthe residue was washed with water
  3. extractionthe aqueous layer was extracted with EA
  4. dry with materialthe combined organic layer was dried over Na2SO4
  5. concentrationconcentrated
  6. customthe residue was purified by silica gel chromatography (PE:EA=5:1)

Sources & evidence

ORD record
ord-f8af03b5a9664d96a06ba5db7945ea2d
Source dataset
uspto-grants-2015_11
Patent number
US09181288B2

Reaction notes

Loading…