1-Hydroxybenzotriazole → 2-(2-Morpholin-4-yl-2-oxo-ethyl)-2-(3-phenyl-propyl)-malonic acid monoethyl ester

HRID 1830204Notes

Reaction equation

HRID 1830204 reaction equation
[CH:1]1(N=C=N)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.N1(C(=O)CC(=C)[C:19]([OH:21])=[O:20])CCOCC1.C1C=CC2N([OH:33])N=NC=2C=1.O1C2C=CC=CC=2N=C1[C:43]([C@@H:45]([NH:49][C:50](=O)[CH:51](CS(CC1C=CC=CC=1C(F)(F)F)(=O)=O)CS(CC1C=CC=CC=1C(F)(F)F)(=O)=O)CCC)=[O:44].CCN([CH:89]([CH3:91])C)C(C)C.CC(OI1(OC(C)=O)(OC(C)=O)[O:105][C:103](=[O:104])[C:102]2[CH:101]=[CH:100][CH:99]=[CH:98][C:97]1=2)=O>C(Cl)Cl>[CH2:89]([O:21][C:19](=[O:20])[C:102]([CH2:97][C:98]([N:49]1[CH2:45][CH2:43][O:44][CH2:51][CH2:50]1)=[O:33])([CH2:101][CH2:100][CH2:99][C:1]1[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1)[C:103]([OH:105])=[O:104])[CH3:91]

Participants

8

Reactant 6

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 159087TriacetoxyperiodinaneHCID 10212428N-[(S)-1-(1-Benzooxazol-2-yl-methanoyl)-butyl]-3-(2-trifluoromethyl-benzylsulfonyl)-2-(2-trifluoromethyl-benzylsulfonylmethyl)-propionamideHCID 12048208N-CyclohexylcarbodiimideHCID 220540222-Methylene4-morpholin-4-yl-4-oxo-butyric acid

Product 1

HCID 210256902-(2-Morpholin-4-yl-2-oxo-ethyl)-2-(3-phenyl-propyl)-malonic acid monoethyl ester

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a stirring suspension of N-Cyclohexylcarbodiimide, N′-methyl polystyrene resin (1.7 mmole/gram, 0.2353 g, 0.4 mmol) in 10 ml of methylene chloride was added the acid 1 (64.3 mg, 0.2 mmol) and HOBT (45.9 mg, 0.34 mmol) which was allowed to stir for 15 minutes at room temperature. Compound 2 (53.75 mg, 0.2 mmol) and DIEA (0.068 ml, 0.4 mmol) were added and the reaction was allowed to stir for 5 hours at room temperature. Then silicycle triamine™ (0.28 g, 1.0 mmol) was added and the reaction was stirred overnight at room temperature. The reaction was filtered and the solvent was removed under reduced pressure. The crude product 3 was used without further purification. Crude compound 3 was dissolved in methylene chloride and Dess-Martin reagent (15% in methylene chloride, 1.13 g, 0.6 mmol) was added and the reaction was allowed to stir at room temperature for 3 hours. The excess Dess-Martin reagent was consumed by adding sodium thiosulfate in saturated sodium bicarbonate. The product was extracted with ethyl acetate and washed with brine. The organic layer was dried over magnesium sulfate, filtered and concentrated under reduced pressure. The product was purified using HPLC to yield 25.7 mg of final compound 4; LCMS retention time 2:89 minutes, M+1(534.4).

Workup

  1. stirringto stir for 5 hours at room temperature
  2. stirringthe reaction was stirred overnight at room temperature
  3. filtrationThe reaction was filtered
  4. customthe solvent was removed under reduced pressure
  5. customThe crude product 3 was used without further purification
  6. dissolutionCrude compound 3 was dissolved in methylene chloride
  7. stirringto stir at room temperature for 3 hours
  8. customThe excess Dess-Martin reagent was consumed
  9. additionby adding sodium thiosulfate in saturated sodium bicarbonate
  10. extractionThe product was extracted with ethyl acetate
  11. washwashed with brine
  12. dry with materialThe organic layer was dried over magnesium sulfate
  13. filtrationfiltered
  14. concentrationconcentrated under reduced pressure
  15. customThe product was purified

Sources & evidence

ORD record
ord-994a14d705e84ca39ea08efd85cba53e
Source dataset
uspto-grants-2006_06
Patent number
US07064123B1

Reaction notes

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