Ethyl Acetate → (5R)-3-[4-(1,1-Dioxo-2,5-dihydrothien-3-yl)-3-fluorophenyl]-5-[4-methyl-1,2,3-triazol-1-ylmethyl]oxazolidin-2-one

HRID 1452568노트

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HRID 1452568 반응식
[F:1][C:2]1[CH:3]=[C:4]([N:9]2[CH2:13][C@H:12]([CH2:14][N:15]3[CH:19]=[C:18]([CH3:20])[N:17]=[N:16]3)[O:11][C:10]2=[O:21])[CH:5]=[CH:6][C:7]=1I.[O:22]=[S:23]1(=[O:45])[CH2:28][CH:27]=[C:26](C2C(F)=CC(N3C[C@H](CN)OC3=O)=CC=2F)C[CH2:24]1.[F-].[K+].C(OCC)(=O)C>CN1CCCC1=O.[Cu]I.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>[O:45]=[S:23]1(=[O:22])[CH2:24][CH:26]=[C:27]([C:7]2[CH:6]=[CH:5][C:4]([N:9]3[CH2:13][C@H:12]([CH2:14][N:15]4[CH:19]=[C:18]([CH3:20])[N:17]=[N:16]4)[O:11][C:10]3=[O:21])=[CH:3][C:2]=2[F:1])[CH2:28]1

참가 물질

8

반응물 4

HCID 8857Ethyl AcetateHCID 522689Potassium FluorideHCID 57526977(5S)-3-[4-(1,1-Dioxo-3,6-dihydro-2H-thiopyran-4-yl)-3,5-difluorophenyl]-5-(aminomethyl)-oxazolidin-2-oneHCID 58778315(5R)-3-(3-Fluoro-4-iodophenyl)-5-[4-methyl-1,2,3-triazol-1-ylmethyl]oxazolidin-2-one2회

생성물 1

HCID 57527012(5R)-3-[4-(1,1-Dioxo-2,5-dihydrothien-3-yl)-3-fluorophenyl]-5-[4-methyl-1,2,3-triazol-1-ylmethyl]oxazolidin-2-one수율 10.2%

시약·촉매·용매 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)촉매HCID 178418397HCID 178418397, 화합물촉매HCID 13387N-methyl-2-pyrrolidone용매2회

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온도
40 °C

실험 절차

(5R)-3-(3-Fluoro-4-iodophenyl)-5-[4-methyl-1,2,3-triazol-1-ylmethyl]oxazolidin-2-one (Intermediate 13) (200 mg, 0.50 mmol) and copper (I) iodide (39 mg, 0.20 mmol) were dissolved in dry 1-methyl-2-pyrrolidinone (2 ml) and the reaction mixture placed under an atmosphere of argon. TetrakiS(triphenylphosphine)palladium(0) (35 mg, 0.05 mmol) was added, followed by a solution of tributyl(1,1-dioxo-2,5-dihydrothien-3-yl)stannane [Bew, Sean P.; Sweeney, J. B., Synthesis (1994), (7), p698] (263 mg, 0.65 mmol) in 1-methyl-2-pyrrolidinone (2 ml) and the reaction mixture stirred for 5 days at 40° C. Aqueous potassium fluoride 1M (150 ml) and ethyl acetate (150 ml) were added and the insoluble materials filtered off. The ethyl acetate layer was separated, dried over magnesium sulphate, filtered then concentrated in vacuo onto Isolute HM-N (2 g). Purification by chromatography on silica gel with 1.5% methanol in dichloromethane gave 20 mg (10%) of the desired compound.

후처리

  1. filtrationthe insoluble materials filtered off
  2. customThe ethyl acetate layer was separated
  3. dry with materialdried over magnesium sulphate
  4. filtrationfiltered
  5. concentrationthen concentrated in vacuo onto Isolute HM-N (2 g)
  6. customPurification by chromatography on silica gel with 1.5% methanol in dichloromethane

출처 및 근거

ORD 기록
ord-e2343ad8696141e298fcfb6a70a90c43
출처 데이터셋
uspto-grants-2009_01
특허 번호
US07473699B2

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