Water → 3-(4-(1-(2(S),3-Dihydroxypropanoyl)-1,2,5,6tetrahydropyrid-4-yl)-3,5-difluorophenyl)-5(S)-(3-methylisoxazol-5-ylaminomethyl)oxazolidin-2-one

HRID 1582356Notes

Reaction equation

HRID 1582356 reaction equation
CC1(C)[O:6][C@H:5]([C:7]([N:9]2[CH2:14][CH2:13][C:12]([C:15]3[C:20]([F:21])=[CH:19][C:18]([N:22]4[CH2:26][C@H:25]([CH2:27][N:28]([C:36]5[O:40][N:39]=[C:38]([CH3:41])[CH:37]=5)C(OC(C)(C)C)=O)[O:24][C:23]4=[O:42])=[CH:17][C:16]=3[F:43])=[CH:11][CH2:10]2)=[O:8])[CH2:4][O:3]1.FC(F)(F)C(O)=O.O>ClCCl>[OH:6][C@@H:5]([CH2:4][OH:3])[C:7]([N:9]1[CH2:14][CH2:13][C:12]([C:15]2[C:20]([F:21])=[CH:19][C:18]([N:22]3[CH2:26][C@H:25]([CH2:27][NH:28][C:36]4[O:40][N:39]=[C:38]([CH3:41])[CH:37]=4)[O:24][C:23]3=[O:42])=[CH:17][C:16]=2[F:43])=[CH:11][CH2:10]1)=[O:8]

Participants

5

Reactant 3

HCID 962WaterHCID 6422Trifluoroacetic acidHCID 571741763-(4-(1-(2,2-Dimethyl-1,3-dioxolan-4(S)-ylcarbonyl)-1,2,5,6-tetrahydropyrid-4-yl)-3,5-difluorophenyl)-5(R)(N-(t-butoxycarbonyl)-3-methylisoxazol-5-ylaminomethyl)oxazolidin-2-one

Product 1

HCID 695848453-(4-(1-(2(S),3-Dihydroxypropanoyl)-1,2,5,6tetrahydropyrid-4-yl)-3,5-difluorophenyl)-5(S)-(3-methylisoxazol-5-ylaminomethyl)oxazolidin-2-oneYield 58.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

3-(4-(1-(2,2-Dimethyl-1,3-dioxolan-4(S)-ylcarbonyl)-1,2,5,6-tetrahydropyrid-4-yl)-3,5-difluorophenyl)-5(R)-(N-(t-butoxycarbonyl)-3-methylisoxazol-5-ylaminomethyl)oxazolidin-2-one (400 mg, 0.65 mM) was dissolved in dichloromethane (6 ml) and treated with trifluoroacetic acid (6 ml) at 0°. After stirring for 30 minutes at ambient temperature, water (1.2 ml) was added, and stirring continued for 1 hour. Solvent was removed, the residue dissolved in methanol (20 ml), and treated with aqueous ammonia to bring the pH to 7-8; solvent was removed, and the residue chromatographed on a 10 g silica Mega Bond Elut® column, eluting with a gradient increasing in polarity from 0 to 5% methanol in dichloromethane. Relevant fractions were combined and evaporated to give the desired product (181 mg ). NMR (DMSO-d6) δ: 2.02 (s, 3H); 2.29 (m, 1H); 2.35 (m, 1H); 3.41 (t, 2H); 3.47 (m, 1H); 3.54 (m, 1H); 3.71 (m, 1H); 3.75 (dd, 1H); 4.04 (dd, 1H); 4.08 (m, 1H); 4.13 (t, 1H); 4.24 (m, 1H); 4.36 (t, 1H); 4.66 (t, 1H); 4.82 (m, 1H); 4.95 (t, 1H); 4.99 (s, 1H); 5.85 (s, 1H); 7.30 (d, 2H); 7.36 (t, 1H). MS (ESP): 479 (MH+) for C22H24F2N4O6

Workup

  1. stirringstirring
  2. waitcontinued for 1 hour
  3. customSolvent was removed
  4. dissolutionthe residue dissolved in methanol (20 ml)
  5. additiontreated with aqueous ammonia
  6. customsolvent was removed
  7. customthe residue chromatographed on a 10 g silica Mega Bond Elut® column
  8. washeluting with
  9. temperaturea gradient increasing in polarity from 0 to 5% methanol in dichloromethane
  10. customevaporated

Sources & evidence

ORD record
ord-57b0aeff66a64df8897355be7ab2f89e
Source dataset
uspto-grants-2004_05
Patent number
US06734200B1

Reaction notes

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