4-(2-Propyn-1-yl)morpholine → {4-[3-[2-(4-Chloro-phenyl)-ethoxy]-5-(3-morpholin-4-yl-prop-1-ynyl)phenylsulfanyl]-2-methyl-phenoxy}-acetic Acid Ethyl Ester

HRID 1513159

Reaction equation

HRID 1513159 reaction equation
[CH2:1]([O:3][C:4](=[O:32])[CH2:5][O:6][C:7]1[CH:12]=[CH:11][C:10]([S:13][C:14]2[CH:19]=[C:18]([O:20][CH2:21][CH2:22][C:23]3[CH:28]=[CH:27][C:26]([Cl:29])=[CH:25][CH:24]=3)[CH:17]=[C:16](Br)[CH:15]=2)=[CH:9][C:8]=1[CH3:31])[CH3:2].[CH2:33]([N:36]1[CH2:41][CH2:40][O:39][CH2:38][CH2:37]1)[C:34]#[CH:35]>C(N(CC)CC)C.CN(C=O)C.[Pd](Cl)Cl.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[Cu](I)I>[CH2:1]([O:3][C:4](=[O:32])[CH2:5][O:6][C:7]1[CH:12]=[CH:11][C:10]([S:13][C:14]2[CH:15]=[C:16]([C:35]#[C:34][CH2:33][N:36]3[CH2:41][CH2:40][O:39][CH2:38][CH2:37]3)[CH:17]=[C:18]([O:20][CH2:21][CH2:22][C:23]3[CH:28]=[CH:27][C:26]([Cl:29])=[CH:25][CH:24]=3)[CH:19]=2)=[CH:9][C:8]=1[CH3:31])[CH3:2]

Participants

7

Reactant 2

HCID 4129414-(2-Propyn-1-yl)morpholineHCID 57791905(4-{3-Bromo-5-[2-(4-chloro-phenyl)-ethoxy]-phenylsulfanyl}-2-methyl-phenoxy)acetic acid ethyl ester

Product 1

HCID 67171037{4-[3-[2-(4-Chloro-phenyl)-ethoxy]-5-(3-morpholin-4-yl-prop-1-ynyl)phenylsulfanyl]-2-methyl-phenoxy}-acetic Acid Ethyl Ester

Reagents, catalysts & solvents 4

HCID 83717Copper iodideCatalystHCID 6102075Dichlorobis(triphenylphosphine)palladiumCatalystHCID 6228DimethylformamideSolventHCID 8471TriethylamineSolvent

Procedure

(4-{3-Bromo-5-[2-(4-chloro-phenyl)-ethoxy]-phenylsulfanyl}-2-methyl-phenoxy)-acetic acid ethyl ester (300 mg; 0.56 mmol), 4-prop-2-ynyl-morpholine (280.4 mg; 2.2 mmol), bis(triphenylphosphine) palladium (II) chloride (31.4 mg; 0.045 mmol) and copper iodide (6.4 mg; 0.034 mmol) were dissolved in a mixture of triethylamine (2 mL) and DMF (2 mL) under an atmosphere of nitrogen. The reaction mixture was reacted in a microwave oven at 110° C. for 1.5 h. The reaction mixture was evaporated to dryness, and 5% aqueous citric acid (30 mL) and ethyl acetate (30 mL) was added. The two phases were separated and the aqueous phase was extracted with ethyl acetate (30 mL). The combined organic phases were dried and evaporated to dryness and purified by preparative HPLC (method B). Yield: 300 mg; 92%. HPLC-MS: m/z: 580.7 (M+H)+; Rt: 2.16 min.

Workup

  1. customThe reaction mixture was reacted in a microwave oven at 110° C. for 1.5 h
  2. customThe reaction mixture was evaporated to dryness, and 5% aqueous citric acid (30 mL) and ethyl acetate (30 mL)
  3. additionwas added
  4. customThe two phases were separated
  5. extractionthe aqueous phase was extracted with ethyl acetate (30 mL)
  6. customThe combined organic phases were dried
  7. customevaporated to dryness
  8. custompurified by preparative HPLC (method B)

Sources & evidence

ORD record
ord-6b756e2ee4df496fa42d82629d604c68
Source dataset
uspto-grants-2012_07
Patent number
US08217086B2

Linked notes

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