Dicyclohexylcarbodiimide → 3-(4-(4-(2-Phenyl-1,3-dioxan-5-ylcarbonyl)piperazin-1-yl)-3-fluorophenyl)-5(R)-(isoxazol-3-yloxymethyl)oxazolidin-2-one

HRID 1167437Notes

Reaction equation

HRID 1167437 reaction equation
[C:1]1([CH:7]2[O:12][CH2:11][CH:10]([C:13]([OH:15])=O)[CH2:9][O:8]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.ON1C(=O)CCC1=O.C1(N=C=NC2CCCCC2)CCCCC1.C(N(CC)C(C)C)(C)C.Cl.Cl.[N:50]1([C:56]2[CH:61]=[CH:60][C:59]([N:62]3[CH2:66][C@H:65]([CH2:67][O:68][C:69]4[CH:73]=[CH:72][O:71][N:70]=4)[O:64][C:63]3=[O:74])=[CH:58][C:57]=2[F:75])[CH2:55][CH2:54][NH:53][CH2:52][CH2:51]1>ClCCl>[C:1]1([CH:7]2[O:8][CH2:9][CH:10]([C:13]([N:53]3[CH2:52][CH2:51][N:50]([C:56]4[CH:61]=[CH:60][C:59]([N:62]5[CH2:66][C@H:65]([CH2:67][O:68][C:69]6[CH:73]=[CH:72][O:71][N:70]=6)[O:64][C:63]5=[O:74])=[CH:58][C:57]=4[F:75])[CH2:55][CH2:54]3)=[O:15])[CH2:11][O:12]2)[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1

Participants

7

Reactant 5

HCID 10868DicyclohexylcarbodiimideHCID 80170N-HydroxysuccinimideHCID 81531DiisopropylethylamineHCID 105844682-phenyl-1,3-dioxane-5-carboxylic AcidHCID 69980303HCID 69980303, compound

Product 1

HCID 543077073-(4-(4-(2-Phenyl-1,3-dioxan-5-ylcarbonyl)piperazin-1-yl)-3-fluorophenyl)-5(R)-(isoxazol-3-yloxymethyl)oxazolidin-2-oneYield 70%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of 2-phenyl-1,3-dioxan-5-ylcarboxylic acid (478 mg, 2.3 mmol) and N-hydroxysuccinimide (291 mg, 2.5 mmol) in anhydrous dichloromethane (25 ml) at 0° was added dicyclohexylcarbodiimide (522 mg, 2.5 mmol). After sitting 1 hour at 0°, N,N-diisopropylethylamine (623 mg, 4.8 mmol) was added, followed by 3-(4-(piperazin-1-yl)-3-fluorophenyl)-5(R)-(isoxazol-3-yloxymethyl)oxazolidin-2-one dihydrochloride (1 g, 2.3 mmol) in portions over 5 minutes. The temperature was allowed to rise to ambient, and stirring continued for 3 hours. Solid was filtered off, washed with dichloromethane (2×20 ml), and the combined organics evaporated to dryness. The residue was purified by chromatography on a 20 g silica Mega Bond Elut® column, eluting with a gradient increasing in polarity from 0 to 10% MeOH in dichloromethane. Relevant fractions were combined and evaporated to give the required product (890 mg) as a mixture of cis and trans isomers.

Workup

  1. waitcontinued for 3 hours
  2. filtrationSolid was filtered off
  3. washwashed with dichloromethane (2×20 ml)
  4. customthe combined organics evaporated to dryness
  5. customThe residue was purified by chromatography on a 20 g silica Mega Bond Elut® column
  6. washeluting with
  7. temperaturea gradient increasing in polarity from 0 to 10% MeOH in dichloromethane
  8. customevaporated

Sources & evidence

ORD record
ord-bb05f1dd79d54726a82f0cb598dc35bd
Source dataset
uspto-grants-2003_09
Patent number
US06617339B1

Reaction notes

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