Trimethylaluminum → (S)-N-[5-(4-chlorophenoxy)pyrazin-2-yl]-4-hydroxy-4-(3-methoxyphenyl)butanamide

HRID 1972244Notes

Reaction equation

HRID 1972244 reaction equation
[Cl:1][C:2]1[CH:15]=[CH:14][C:5]([O:6][C:7]2[N:8]=[CH:9][C:10]([NH2:13])=[N:11][CH:12]=2)=[CH:4][CH:3]=1.C[Al](C)C.[CH3:20][O:21][C:22]1[CH:23]=[C:24]([C@H:28]2[O:32][C:31](=[O:33])[CH2:30][CH2:29]2)[CH:25]=[CH:26][CH:27]=1>C(Cl)Cl.C1(C)C=CC=CC=1>[Cl:1][C:2]1[CH:15]=[CH:14][C:5]([O:6][C:7]2[N:8]=[CH:9][C:10]([NH:13][C:31](=[O:33])[CH2:30][CH2:29][C@H:28]([OH:32])[C:24]3[CH:25]=[CH:26][CH:27]=[C:22]([O:21][CH3:20])[CH:23]=3)=[N:11][CH:12]=2)=[CH:4][CH:3]=1

Participants

6

Reactant 3

HCID 16682925TrimethylaluminumHCID 57202694(S)-dihydro-5-(3-methoxyphenyl)furan-2(3H)-oneHCID 594857965-(4-Chlorophenoxy)pyrazin-2-amine

Product 1

HCID 59485666(S)-N-[5-(4-chlorophenoxy)pyrazin-2-yl]-4-hydroxy-4-(3-methoxyphenyl)butanamideYield 100.1%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 6344DichloromethaneSolvent2×

Procedure

To a stirred solution of 5-(4-chlorophenoxy)pyrazin-2-amine (149 mg, 0.67 mmol) in dry CH2Cl2 (1.5 mL) at room temperature, under argon, is added trimethylaluminum (0.335 mL of a 2.0 N solution in toluene, 0.67 mmol) dropwise. The resulting mixture is stirred for 15 min, then (S)-dihydro-5-(3-methoxyphenyl)furan-2(3H)-one (107 mg, 0.555 mmol) in CH2Cl2 (1.5 mL) is added slowly and stirring is continued at ambient temperature for 3 days. The reaction is quenched carefully with 10% aqueous citric acid (0.5 mL) at 0° C. The mixture is then partitioned between saturated aqueous NaHCO3 (10 mL) and CH2Cl2 (10 mL). The aqueous layer is extracted further with CH2Cl2 (3×10 mL). The combined organic extracts are dried over Na2SO4, filtered, and concentrated in vacuo. The residue is then purified on silica gel (0-75% ethyl acetate in hexane) to give (S)—N-[5-(4-chlorophenoxy)pyrazin-2-yl]-4-hydroxy-4-(3-methoxyphenyl)butanamide (230 mg, 100%) as a white solid.

Workup

  1. stirringstirring
  2. waitis continued at ambient temperature for 3 days
  3. customThe reaction is quenched carefully with 10% aqueous citric acid (0.5 mL) at 0° C
  4. customThe mixture is then partitioned between saturated aqueous NaHCO3 (10 mL) and CH2Cl2 (10 mL)
  5. extractionThe aqueous layer is extracted further with CH2Cl2 (3×10 mL)
  6. dry with materialThe combined organic extracts are dried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe residue is then purified on silica gel (0-75% ethyl acetate in hexane)

Sources & evidence

ORD record
ord-fc6dd9d2d74d4158acf3d83199ac9298
Source dataset
uspto-grants-2013_04
Patent number
US08431607B2

Reaction notes

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