Dicyclohexylcarbodiimide → 3-(4-(4-((2S,4R)-1-Acetyl-4-hydroxy-2-pyrrolidinylcarbonyl)-piperazin-1-yl)-3-fluorophenyl)-5(R)-(isoxazol-3-yloxymethyl)oxazolidin-2-one

HRID 1167448Notes

Reaction equation

HRID 1167448 reaction equation
[C:1]([N:4]1[CH2:8][C@H:7]([OH:9])[CH2:6][C@H:5]1[C:10]([OH:12])=O)(=[O:3])[CH3:2].C1(N=C=NC2CCCCC2)CCCCC1.ON1C2C=CC=CC=2N=N1.Cl.Cl.[N:40]1([C:46]2[CH:51]=[CH:50][C:49]([N:52]3[CH2:56][C@H:55]([CH2:57][O:58][C:59]4[CH:63]=[CH:62][O:61][N:60]=4)[O:54][C:53]3=[O:64])=[CH:48][C:47]=2[F:65])[CH2:45][CH2:44][NH:43][CH2:42][CH2:41]1.C(N(CC)C(C)C)(C)C>ClCCl.CN(C=O)C>[C:1]([N:4]1[CH2:8][C@H:7]([OH:9])[CH2:6][C@H:5]1[C:10]([N:43]1[CH2:42][CH2:41][N:40]([C:46]2[CH:51]=[CH:50][C:49]([N:52]3[CH2:56][C@H:55]([CH2:57][O:58][C:59]4[CH:63]=[CH:62][O:61][N:60]=4)[O:54][C:53]3=[O:64])=[CH:48][C:47]=2[F:65])[CH2:45][CH2:44]1)=[O:12])(=[O:3])[CH3:2]

Participants

8

Reactant 5

HCID 10868DicyclohexylcarbodiimideHCID 65784OxaceprolHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 69980303HCID 69980303, compound

Product 1

HCID 699806263-(4-(4-((2S,4R)-1-Acetyl-4-hydroxy-2-pyrrolidinylcarbonyl)-piperazin-1-yl)-3-fluorophenyl)-5(R)-(isoxazol-3-yloxymethyl)oxazolidin-2-one

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent2×

Procedure

A suspension of (2S,4R)-1-acetyl-4-hydroxy-2-pyrrolidinecarboxylic acid (173 mg, 1 mmol) in dichloromethane (10 ml) and DMF (2 ml) under nitrogen was treated successively with dicyclohexylcarbodiimide (227 mg, 1.1 mmol) and 1-hydroxybenzotriazole (149 mg, 1.1 mmol), then stirred at ambient temperature for 1 hour. A solution of 3-(4-(piperazin-1-yl)-3-fluorophenyl)-5(R)-(isoxazol-3-yloxymethyl)oxazolidin-2-one dihydrochloride (435 mg, 1 mmol) and N,N-diisopropylethylamine (258 mg, 2 mmol) in dichloromethane (5 ml) was added, and the mixture stirred for 18 hours. Solid was filtered off, the organic solution evaporated to dryness, and the residue purified by chromatography on a 10 g silica Mega Bond Elut® column, eluting with a gradient increasing in polarity from 0 to 15% MeOH in dichloromethane. Relevant fractions were combined and evaporated to give the desired product after trituration with diethyl ether (210 mg).

Workup

  1. stirringthe mixture stirred for 18 hours
  2. filtrationSolid was filtered off
  3. customthe organic solution evaporated to dryness
  4. customthe residue purified by chromatography on a 10 g silica Mega Bond Elut® column
  5. washeluting with
  6. temperaturea gradient increasing in polarity from 0 to 15% MeOH in dichloromethane
  7. customevaporated

Sources & evidence

ORD record
ord-2db109fa1c1e403cb70251ae643ee528
Source dataset
uspto-grants-2003_09
Patent number
US06617339B1

Reaction notes

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