Triphenylarsine → (S)-(-)-4-[4-[5-[(acetylamino)methyl]-2-oxo-3-oxazolidinyl]-2-fluorophenyl]-3,6-dihydro-1(2H)-pyridinecarboxylic acid 1,1-dimethylethyl ester

HRID 428754노트

반응식

HRID 428754 반응식
C[Sn](C)(C)[C:3]1[CH:8]=[CH:7][C:6]([N:9]2[CH2:13][C@H:12]([CH2:14][NH:15][C:16](=[O:18])[CH3:17])[O:11][C:10]2=[O:19])=[CH:5][C:4]=1[F:20].[CH3:23][C:24]([O:27][C:28]([N:30]1[CH2:35][CH:34]=[C:33](OS(C(F)(F)F)(=O)=O)[CH2:32][CH2:31]1)=[O:29])([CH3:26])[CH3:25].C1([As](C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>CN1CCCC1=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]>[CH3:26][C:24]([O:27][C:28]([N:30]1[CH2:31][CH:32]=[C:33]([C:3]2[CH:8]=[CH:7][C:6]([N:9]3[CH2:13][C@H:12]([CH2:14][NH:15][C:16](=[O:18])[CH3:17])[O:11][C:10]3=[O:19])=[CH:5][C:4]=2[F:20])[CH2:34][CH2:35]1)=[O:29])([CH3:23])[CH3:25]

참가 물질

6

반응물 3

HCID 11773TriphenylarsineHCID 10991161Tert-butyl 4-(trifluoromethanesulfonyloxy)-1,2,3,6-tetrahydropyridine-1-carboxylateHCID 11304566N-({(5S)-3-[3-Fluoro-4-(trimethylstannyl)phenyl]-2-oxo-1,3-oxazolidin-5-yl}methyl)acetamide

생성물 1

HCID 18716141(S)-(-)-4-[4-[5-[(acetylamino)methyl]-2-oxo-3-oxazolidinyl]-2-fluorophenyl]-3,6-dihydro-1(2H)-pyridinecarboxylic acid 1,1-dimethylethyl ester

시약·촉매·용매 2

HCID 9811564Bis(dibenzylideneacetone)palladium촉매HCID 13387N-methyl-2-pyrrolidone용매

실험 절차

A mixture of (S)-(−)-N-[[3-[4-trimethylstannyl-3-fluorophenyl]-2-oxo-5-oxazolidinyl]methyl]acetamide (690 mg), 3,6-dihydro-4-[[(trifluoromethyl)sulfonyl]oxy]-1(2H)-pyridinecarboxylic acid 1,1-dimethylethyl ester (step 2 of EXAMPLE 20, 500mg), tris(dibenzylideneacetone)dipalladium(0) (14 mg) and triphenylarsine (37 mg) in N-methyl-2-pyrrolidinone (7.5 mL) is degassed, stirred under N2 at ambient temperature for 4.5 days, diluted with ethyl acetate, washed with water (3×40 mL) and saline (20 mL), dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue is chromatographed on silica gel (230-400 mesh, 120g), eluting with a gradient of methanol/methylene chloride (1/99-2/98), and those fraction having an Rf=0.27 by TLC (methanol/chloroform, 2×5/95) are pooled and concentrated to give the title compound, 1H NMR (CDCl3, 400 MHz) 7.39, 7.22, 7.13, 7.01, 5.92, 4.82, 4.06, 3.80, 3.67, 3.61, 2.47, 2.03, 1.49 δ.

후처리

  1. customis degassed
  2. additiondiluted with ethyl acetate
  3. washwashed with water (3×40 mL) and saline (20 mL)
  4. dry with materialdried over anhydrous magnesium sulfate
  5. concentrationconcentrated under reduced pressure
  6. customThe residue is chromatographed on silica gel (230-400 mesh, 120g)
  7. washeluting with a gradient of methanol/methylene chloride (1/99-2/98)
  8. concentrationconcentrated

출처 및 근거

ORD 기록
ord-31b003e15f3947248db5aa8cb5e96b14
출처 데이터셋
uspto-grants-2001_11
특허 번호
US06313307B1

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