4-Methylmorpholine → N-[(2E)-2-hydroxyimino-2-[3-[(2-methylpropan-2-yl)oxy]propanoylamino]-1-phenylethyl]-3-(4-phenylphenyl)sulfonyl-1,3-thiazolidine-2-carboxamide

HRID 1964845Notes

Reaction equation

HRID 1964845 reaction equation
[C:1]([O:5][CH2:6][CH2:7][C:8]([OH:10])=O)([CH3:4])([CH3:3])[CH3:2].CN1CCOCC1.ClC(OCC(C)C)=O.[NH2:26]/[C:27](=[N:58]\[OH:59])/[C@H:28]([NH:35][C:36]([CH:38]1[N:42]([S:43]([C:46]2[CH:51]=[CH:50][C:49]([C:52]3[CH:57]=[CH:56][CH:55]=[CH:54][CH:53]=3)=[CH:48][CH:47]=2)(=[O:45])=[O:44])[CH2:41][CH2:40][S:39]1)=[O:37])[C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1>C1COCC1>[C:49]1([C:52]2[CH:57]=[CH:56][CH:55]=[CH:54][CH:53]=2)[CH:50]=[CH:51][C:46]([S:43]([N:42]2[CH2:41][CH2:40][S:39][CH:38]2[C:36]([NH:35][CH:28]([C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)/[C:27](/[NH:26][C:8](=[O:10])[CH2:7][CH2:6][O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[N:58]\[OH:59])=[O:37])(=[O:45])=[O:44])=[CH:47][CH:48]=1

Participants

6

Reactant 4

HCID 79724-MethylmorpholineHCID 62365Isobutyl chloroformateHCID 27609493-(tert-Butoxy)propionic acidHCID 87519173N-[(1R,2Z)-2-amino-2-hydroxyimino-1-phenylethyl]-3-(4-phenylphenyl)sulfonyl-1,3-thiazolidine-2-carboxamide

Product 1

HCID 136348958N-[(2E)-2-hydroxyimino-2-[3-[(2-methylpropan-2-yl)oxy]propanoylamino]-1-phenylethyl]-3-(4-phenylphenyl)sulfonyl-1,3-thiazolidine-2-carboxamideYield 86%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-15 °C

Procedure

Carboxylic acid, e.g., 3-tert-butoxypropionic acid (35 mg, 0.24 mmol), was dissolved in THF (2 mL). The resulting solution was cooled down to −15° C. NMM (84 μL, 0.76 mmol), followed by isobutyl chloroformate (33 μL, 0.25 mmol), were added. The mixture was stirred at −15° C. for 30 min. Intermediate Id, e.g. N-[(1R,2Z)-2-amino-2-(hydroxyimino)-1-phenylethyl]-3-(biphenyl-4-ylsulfonyl)-1,3-thiazolidine-2-carboxamide (108 mg, 0.22 mmol) in THF (2 mL) was added dropwise. The mixture was stirred overnight, letting the temperature increasing up to RT. Solvents were evaporated. The resulting oil was dissolved in AcOEt, and washed with sat NH4Cl and sat NaHCO3. Aqueous phases were extracted with two portions of AcOEt. Combined organic phases were dried over MgSO4, filtrated and evaporated, affording intermediate Id′, e.g. 3-(biphenyl-4-ylsulfonyl)-N-[(2E)-2-[(3-tert-butoxypropanoyl)amino]-2-(hydroxyimino)-1-phenylethyl]-1,3-thiazolidine-2-carboxamide (118 mg, 86% yield), which was directly used in the next step.

Workup

  1. additionwere added
  2. stirringThe mixture was stirred overnight
  3. temperatureincreasing up to RT
  4. customSolvents were evaporated
  5. dissolutionThe resulting oil was dissolved in AcOEt
  6. washwashed
  7. extractionAqueous phases were extracted with two portions of AcOEt
  8. dry with materialCombined organic phases were dried over MgSO4
  9. filtrationfiltrated
  10. customevaporated

Sources & evidence

ORD record
ord-b3e87ef686a44b979bfc0fa679bf4d69
Source dataset
uspto-grants-2013_04
Patent number
US08415480B2

Reaction notes

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