Tributylphosphine → 5(s)-(1,2,4-Oxadiazol-3-yl-aminomethyl)-3-(3,5-difluoro-4-(1-(2(s),3-dihydroxypropanoyl)-1,2,5,6-tetrahydropyrid-4-yl)phenyl)oxazolidin-2-one

HRID 1582369Notes

Reaction equation

HRID 1582369 reaction equation
[OH:1][C@@H:2]([CH2:33][OH:34])[C:3]([N:5]1[CH2:10][CH2:9][C:8]([C:11]2[C:16]([F:17])=[CH:15][C:14]([N:18]3[CH2:22][C@H:21]([CH2:23][NH:24]C4ON=C(C)C=4)[O:20][C:19]3=[O:31])=[CH:13][C:12]=2[F:32])=[CH:7][CH2:6]1)=[O:4].C(OC(N[C:43]1[N:47]=[CH:46][O:45][N:44]=1)=O)(C)(C)C.C(P(CCCC)CCCC)CCC.N(C(N1CCCCC1)=O)=NC(N1CCCCC1)=O>C1COCC1>[O:45]1[CH:46]=[N:47][C:43]([CH:23]([NH2:24])[C@H:21]2[O:20][C:19](=[O:31])[N:18]([C:14]3[CH:13]=[C:12]([F:32])[C:11]([C:8]4[CH2:9][CH2:10][N:5]([C:3](=[O:4])[C@@H:2]([OH:1])[CH2:33][OH:34])[CH2:6][CH:7]=4)=[C:16]([F:17])[CH:15]=3)[CH2:22]2)=[N:44]1

Participants

6

Reactant 4

HCID 13831TributylphosphineHCID 730421,1'-(Azodicarbonyl)dipiperidineHCID 22014528tert-butyl N-(1,2,4-oxadiazol-3-yl)carbamateHCID 695848453-(4-(1-(2(S),3-Dihydroxypropanoyl)-1,2,5,6tetrahydropyrid-4-yl)-3,5-difluorophenyl)-5(S)-(3-methylisoxazol-5-ylaminomethyl)oxazolidin-2-one

Product 1

HCID 698904365(s)-(1,2,4-Oxadiazol-3-yl-aminomethyl)-3-(3,5-difluoro-4-(1-(2(s),3-dihydroxypropanoyl)-1,2,5,6-tetrahydropyrid-4-yl)phenyl)oxazolidin-2-oneYield 45.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a stirred solution of the appropriate intermediate of Example 20 (600 mg, 1.37 mmol) in anhydrous THF (30 ml) under an atmosphere of nitrogen was added 3-t-butyloxycarbonylamino-1,2,4-oxadiazole (304 mg, 1.64 mmol) and tri-n-butylphosphine (510 μL, 2.05 mmol). The mixture was cooled to 0° C. and 1,1′-(azodicarbonyl)-di-piperidine (518 mg, 2.05 mmol) was added portionwise. The reaction was allowed to warm to room temperature and stir for 18 hours. The THF was removed under reduced pressure and the resulting residue taken into dichloromethane (15 ml) and cooled to 0° C. A white solid precipitated and the solution was filtered and purified by MPLC (Merck 9385 silica, 40-60% ethyl acetate in iso-hexane). The solvent was removed under reduced pressure to give a clear, colourless oil which was triturated with ether to yield the title compound as a fine white powder (291 mg, 35%). 1H-NMR (300 MHz, DMSO-d6): δ=1.31 (d, 6H), 1.47 (s, 9H), 2.27-2.48 (m, 2H), 3.61-4.28 (m, 10H), 4.87-5.02 (m, 2H), 5.89 (broad s, 1H), 7.33 (d, 2H), 9.54 (s, 1H). MS: ESP+ (M+H)+606.

Workup

  1. temperatureto warm to room temperature
  2. customThe THF was removed under reduced pressure
  3. temperaturecooled to 0° C
  4. customA white solid precipitated
  5. filtrationthe solution was filtered
  6. custompurified by MPLC (Merck 9385 silica, 40-60% ethyl acetate in iso-hexane)
  7. customThe solvent was removed under reduced pressure
  8. customto give a clear, colourless oil which
  9. customwas triturated with ether

Sources & evidence

ORD record
ord-94a6e04910794a2d84f661ad66f96785
Source dataset
uspto-grants-2004_05
Patent number
US06734200B1

Reaction notes

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