HCID 10374773, compound → 3-(4-(3(S)-(2(S),3-Dihydroxypropanoyl)pyrrolidin-1-yl)-3-fluorophenyl)-5(S)-(isoxazol-3-ylaminomethyl)oxazolidin-2-one

HRID 1582350Notes

Reaction equation

HRID 1582350 reaction equation
Cl.N[C@H:3]1[CH2:7][CH2:6][N:5]([C:8]2[CH:13]=[CH:12][C:11]([N:14]3[CH2:18][C@H:17]([CH2:19][N:20]([C:29]4[CH:33]=[CH:32][O:31][N:30]=4)C(OCC(Cl)(Cl)Cl)=O)[O:16][C:15]3=[O:34])=[CH:10][C:9]=2[F:35])[CH2:4]1.CC1(C)[O:41][C@H:40]([C:42](Cl)=[O:43])[CH2:39][O:38]1>N1C=CC=CC=1.ClCCl.C(OCC)(=O)C.O>[OH:41][C@@H:40]([CH2:42][OH:43])[C:39]([C@H:3]1[CH2:7][CH2:6][N:5]([C:8]2[CH:13]=[CH:12][C:11]([N:14]3[CH2:18][C@H:17]([CH2:19][NH:20][C:29]4[CH:33]=[CH:32][O:31][N:30]=4)[O:16][C:15]3=[O:34])=[CH:10][C:9]=2[F:35])[CH2:4]1)=[O:38]

Participants

7

Reactant 2

HCID 10374773HCID 10374773, compoundHCID 695849253-(4(3(S) aminopyrrolidin-1-yl)-3-fluorophenyl)-5(R)-(N-(2,2,2-trichloroethyloxycarbonyl)isoxazol-3-ylaminomethyl)oxazolidin-2-one hydrochloride salt

Product 1

HCID 537427063-(4-(3(S)-(2(S),3-Dihydroxypropanoyl)pyrrolidin-1-yl)-3-fluorophenyl)-5(S)-(isoxazol-3-ylaminomethyl)oxazolidin-2-oneYield 143.5%

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 1049PyridineSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

3-(4-(3(S)-Aminopyrrolidin-1-yl)-3-fluorophenyl)-5(R)-(N-(2,2,2-trichloroethyloxycarbonyl)isoxazol-3-ylaminomethyl)oxazolidin-2-one hydrochloride salt (400 mg, 0.698 mM) in pyridine (5 ml) was treated dropwise with a solution of 2,2-dimethyl-1,3-dioxolan-4(S)-ylcarbonyl chloride (200 mg, 1.2 mM) in dichloromethane (2 ml), and the mixture stirred 3 hours at ambient temperature. The mixture was diluted with ethyl acetate (15 ml) and water (15 ml), the organic layer separated, washed with aqueous sodium bicarbonate (10 ml) and brine (10 ml), and evaporated, then azeotroped with toluene (20 ml). The residue was purified by chromatography on a 10 g silica Mega Bond Elut® column, eluting with a gradient increasing in polarity from 0 to 100% ethyl acetate in dichloromethane. Relevant fractions were combined and evaporated to give the desired product (435 mg ). NMR (DMSO-d6) δ: 1.30 (s, 3H); 1.37 (s, 3H); 1.89 (hextet, 1H); 2.13 (hextet, 1H); 3.20 (m, 1H); 3.24 (m overlapped by H2O, ˜1H); 3.39 (m, 1H); 3.48 (m, 1H); 3.82 (dd, 1H); 3.91 (dd, 1H); 4.12 (overlapping m, 3H); 4.33 (t overlapping m, 2H); 4.42 (dd, 2H); 4.97 (d, 1H); 5.02 (m, 1H); 5.06 (d, 1H); 6.75 (t, 1H); 6.87 (d, 1H); 7.08 (dd, 1H); 7.34 (dd, 1H); 7.94 (d, 1H); 8.89 (d, 1H). MS (ESP): 664 (MH+) for C26H29Cl3FN5O8

Workup

  1. customthe organic layer separated
  2. washwashed with aqueous sodium bicarbonate (10 ml) and brine (10 ml)
  3. customevaporated
  4. customazeotroped with toluene (20 ml)
  5. customThe residue was purified by chromatography on a 10 g silica Mega Bond Elut® column
  6. washeluting with
  7. temperaturea gradient increasing in polarity from 0 to 100% ethyl acetate in dichloromethane
  8. customevaporated

Sources & evidence

ORD record
ord-60f8976518734c72bc0496aedeb2b5bd
Source dataset
uspto-grants-2004_05
Patent number
US06734200B1

Reaction notes

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