Citric Acid → [4-(3-Bromo-5-cyclopentylmethoxy-phenylsulfanyl)-2-methyl-phenoxy]-acetic Acid Ethyl Ester

HRID 549553Notes

Reaction equation

HRID 549553 reaction equation
Br[C:2]1[CH:7]=[C:6]([O:8][CH2:9][CH:10]2[CH2:14][CH2:13][CH2:12][CH2:11]2)[CH:5]=[C:4]([Br:15])[CH:3]=1.[CH2:16]([O:18][C:19](=[O:30])[CH2:20][O:21][C:22]1[CH:27]=[CH:26][C:25]([SH:28])=[CH:24][C:23]=1[CH3:29])[CH3:17].CN1C(=O)CCC1.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>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].C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2].C(OCC)(=O)C>[CH2:16]([O:18][C:19](=[O:30])[CH2:20][O:21][C:22]1[CH:27]=[CH:26][C:25]([S:28][C:2]2[CH:7]=[C:6]([O:8][CH2:9][CH:10]3[CH2:14][CH2:13][CH2:12][CH2:11]3)[CH:5]=[C:4]([Br:15])[CH:3]=2)=[CH:24][C:23]=1[CH3:29])[CH3:17]

Participants

8

Reactant 4

HCID 311Citric AcidHCID 13387N-methyl-2-pyrrolidoneHCID 16641178Ethyl (4-mercapto-2-methylphenoxy)acetateHCID 671714831,3-Dibromo-5-(cyclopentylmethoxy)benzene

Product 1

HCID 57791902[4-(3-Bromo-5-cyclopentylmethoxy-phenylsulfanyl)-2-methyl-phenoxy]-acetic Acid Ethyl Ester

Reagents, catalysts & solvents 3

HCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 8857Ethyl AcetateSolvent

Procedure

1,3-Dibromo-5-cyclopentylmethoxy-benzene (2.9 g; 8.6 mmol), (4-Mercapto-2-methyl-phenoxy)-acetic acid ethyl ester (1.5 g; 6.6 mmol), tris(dibenzylideneacetone)dipalladium(0) (0.18 g, 0.20 mmol) and 1,1′-bis(diphenylphosphino)-ferrocen (0.22 g; 0.40 mmol) was added to a dried microwave flask under an atmosphere of nitrogene. The reaction flask was sealed and dry NMP (10 mL) and TEA (3.7 mL; 26.5 mmol) was added through the septum. The reaction flask was reacted in a microwave oven at 140° C. for 1 h. Ethyl acetate (30 mL) and aqueous 5% citric acid (30 mL) was added to the reaction mixture and the phases were separated. The aqueous phase was extracted with ethyl acetate (30 mL×2) and the pooled organic phases were dried (MgSO4) and evaporated to dryness. The reaction mixture was purified by flash chromatography (heptane→heptane:ethyl acetate (9:1½). Yield: 1.45 g (46%). HPLC-MS: m/z: 479.8 (M)+; Rt: 3.18 min.

Workup

  1. customThe reaction flask was sealed
  2. customThe reaction flask was reacted in a microwave oven at 140° C. for 1 h
  3. customthe phases were separated
  4. extractionThe aqueous phase was extracted with ethyl acetate (30 mL×2)
  5. dry with materialthe pooled organic phases were dried (MgSO4)
  6. customevaporated to dryness
  7. customThe reaction mixture was purified by flash chromatography (heptane→heptane:ethyl acetate (9:1½)

Sources & evidence

ORD record
ord-d4ca545aab57407d8d2d6b996a9aaa50
Source dataset
uspto-grants-2011_05
Patent number
US07943669B2

Reaction notes

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