4-Methylmorpholine → HCID 86758065, compound

HRID 1934750Notes

Reaction equation

HRID 1934750 reaction equation
[C:1]([N:9]1[C:13]2([CH2:18][CH2:17][CH:16]([C:19]([NH:21][CH2:22][CH2:23][C:24]([O:26][C:27](=O)[C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=3)=[O:25])=[O:20])[CH2:15][CH2:14]2)[S:12][CH2:11][C@H:10]1[C:35](O)=[O:36])(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl.[CH3:39][O:40][C:41](=[O:48])[C@H:42]([CH2:44][CH2:45][S:46][CH3:47])[NH2:43].O.ON1C2C=CC=CC=2N=N1.CN1CCOCC1.C1(N=C=NC2CCCCC2)CCCCC1>O1CCCC1>[C:1]([N:9]1[C:13]2([CH2:14][CH2:15][CH:16]([C:19]([NH:21][CH2:22][CH2:23][C:24]([O:26][CH2:27][C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=3)=[O:25])=[O:20])[CH2:17][CH2:18]2)[S:12][CH2:11][C@H:10]1[C:35]([NH:43][C@@H:42]([CH2:44][CH2:45][S:46][CH3:47])[C:41]([O:40][CH3:39])=[O:48])=[O:36])(=[O:8])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

7

Reactant 5

HCID 79724-MethylmorpholineHCID 10868DicyclohexylcarbodiimideHCID 27960291-Hydroxybenzotriazole hydrateHCID 11435579L-Methionine, methyl ester, hydrochlorideHCID 86758066HCID 86758066, compound

Product 1

HCID 86758065HCID 86758065, compoundYield 82.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

In 9 ml of anhydrous tetrahydrofuran was dissolved 0.60 g of (3R)-4-benzoyl-8-({[3-(benzoyloxy)-3-oxopropyl]-amino}carbonyl)-1-thia-4-azaspiro[4.5]decane-3-carboxylic acid. At 0-5° C., 0.26 g of L-methionine methyl ester hydrochloride, 0.19 g of 1-hydroxybenzotriazole monohydrate and 0.14 ml of N-methylmorpholine were successively added. After stirring the mixture at the same temperature as above for 30 minutes, 0.27 g of dicyclohexyl carbodiimide was added and the resulting mixture was stirred at the same temperature as above for 30 minutes and then at ambient temperature for 6 hours. The insoluble matter was filtered off, the filtrate was added to a mixture of water and ethyl acetate, pH was adjusted to 2.0 with 2 mol/L hydrochloric acid, and the organic layer was separated. The organic layer was washed successively with water, saturated aqueous solution of sodium hydrogen carbonate and saturated aqueous solution of sodium chloride and dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. Purification of the residue by column chromatography [eluent: toluene:ethyl acetate=1:2] gave 0.62 g of methyl (2S)-2-({[(3R)-4-benzoyl-8-({[3-(benzyloxy)-3-oxopropyl]amino}carbonyl)-1-thia-4-azaspiro[4.5]decan-3-yl]carbonyl}amino)-4-(methylthio)butyrate as a colorless oily product.

Workup

  1. additionwas added
  2. waitat ambient temperature for 6 hours
  3. filtrationThe insoluble matter was filtered off
  4. additionthe filtrate was added to a mixture of water and ethyl acetate, pH
  5. customthe organic layer was separated
  6. washThe organic layer was washed successively with water, saturated aqueous solution of sodium hydrogen carbonate and saturated aqueous solution of sodium chloride
  7. dry with materialdried over anhydrous magnesium sulfate
  8. distillationthe solvent was distilled off under reduced pressure
  9. customPurification of the residue by column chromatography [eluent: toluene:ethyl acetate=1:2]

Sources & evidence

ORD record
ord-61226b539509496787a9b16e10bb3b71
Source dataset
uspto-grants-2002_05
Patent number
US06384065B1

Reaction notes

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