Tributylphosphine → (5S)-3-(4-(1-Benzyl-1,2,5,6-tetrahydropyridin-4-yl)-3-fluorophenyl)-5-(2-oxo-3H-1,3-oxazol-3-ylmethyl)oxazolidin-2-one

HRID 723793

Reaction equation

HRID 723793 reaction equation
[CH2:1]([N:8]1[CH2:13][CH2:12][C:11]([C:14]2[CH:19]=[CH:18][C:17]([N:20]3[CH2:24][C@H:23](CO)[O:22][C:21]3=[O:27])=[CH:16][C:15]=2[F:28])=[CH:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[O:29]1[CH:33]=[CH:32][NH:31][C:30]1=[O:34].[CH2:35](P(CCCC)CCCC)CCC.N(C(N1CCCCC1)=O)=NC(N1CCCCC1)=O>O1CCCC1>[CH2:1]([N:8]1[CH2:13][CH2:12][C:11]([C:14]2[CH:19]=[CH:18][C:17]([N:20]3[CH2:24][C@H:23]([CH2:35][N:31]4[CH:32]=[CH:33][O:29][C:30]4=[O:34])[O:22][C:21]3=[O:27])=[CH:16][C:15]=2[F:28])=[CH:10][CH2:9]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 13831TributylphosphineHCID 730421,1'-(Azodicarbonyl)dipiperidineHCID 1861144-Oxazolin-2-oneHCID 11668069(5R)-3-(4-(1-Benzyl-1,2,5,6-tetrahydropyridin-4-yl)-3-fluorophenyl)-5-hydroxymethyl-oxazolidin-2-one

Product 1

HCID 69365834(5S)-3-(4-(1-Benzyl-1,2,5,6-tetrahydropyridin-4-yl)-3-fluorophenyl)-5-(2-oxo-3H-1,3-oxazol-3-ylmethyl)oxazolidin-2-oneYield 0.9%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

(5R)-3-(4-(1-Benzyl-1,2,5,6-tetrahydropyridin-4-yl)-3-fluorophenyl)-5-hydroxymethyl-oxazolidin-2-one (2.92 g, 7.3 mM; WO 97-30995) was stirred in tetrahydrofuran (60 ml), and 3H-oxazol-2-one (0.69 g, 8.12 mM) and tributylphosphine (1.77 g, 8.75 mM) were added. The mixture was stirred at 0° under nitrogen, and 1,1′-azodicarbonyldipiperidine (2.06 g, 8.18 mM) was added portionwise. The reaction mixture was allowed to warm to ambient temperature and stirred overnight. The precipitate was filtered off and solvent removed. The resulting oil was dissolved in dichloromethane (30 ml), stirred at 0° for 30 minutes, and further precipitate removed. The filtrate was purified by MPLC on silica eluting with a gradient from 60 to 80% ethyl acetate in isohexane, to give a mixture of starting material and product, which was rechromatographed eluting with 3% MeOH in dichloromethane to give the title compound as a white solid (30 mg).

Workup

  1. stirringstirred overnight
  2. filtrationThe precipitate was filtered off
  3. customsolvent removed
  4. dissolutionThe resulting oil was dissolved in dichloromethane (30 ml)
  5. stirringstirred at 0° for 30 minutes
  6. customfurther precipitate
  7. customremoved
  8. customThe filtrate was purified by MPLC on silica eluting with a gradient from 60 to 80% ethyl acetate in isohexane
  9. customto give
  10. additiona mixture of starting material and product, which
  11. customwas rechromatographed
  12. washeluting with 3% MeOH in dichloromethane

Sources & evidence

ORD record
ord-40c12726f9bf4cc4baf4dae825da0c20
Source dataset
uspto-grants-2006_11
Patent number
US07141583B2

Linked notes

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