Triethylamine → HCID 68847889, compound

HRID 1826094Notes

Reaction equation

HRID 1826094 reaction equation
[CH2:1]([CH:3]([CH2:7][C:8]1[CH:13]=[CH:12][C:11]([O:14][CH3:15])=[C:10]([CH2:16][C:17](=[O:29])[NH:18][C:19]2[CH:24]=[CH:23][C:22]([C:25]([F:28])([F:27])[F:26])=[CH:21][CH:20]=2)[CH:9]=1)[C:4](O)=[O:5])[CH3:2].C(N(CC)CC)C.C(Cl)(=O)C(C)(C)C.CC(C)([O-])C.[K+].[CH2:50]([C@H:57]1[CH2:61][O:60][C:59](=[O:62])[NH:58]1)[C:51]1[CH:56]=[CH:55][CH:54]=[CH:53][CH:52]=1>O1CCCC1>[CH2:1]([CH:3]([CH2:7][C:8]1[CH:13]=[CH:12][C:11]([O:14][CH3:15])=[C:10]([CH2:16][C:17](=[O:29])[NH:18][C:19]2[CH:20]=[CH:21][C:22]([C:25]([F:27])([F:26])[F:28])=[CH:23][CH:24]=2)[CH:9]=1)[C:4]([N:58]1[C@@H:57]([CH2:50][C:51]2[CH:52]=[CH:53][CH:54]=[CH:55][CH:56]=2)[CH2:61][O:60][C:59]1=[O:62])=[O:5])[CH3:2]

Participants

7

Reactant 5

HCID 8471TriethylamineHCID 62493Pivaloyl chlorideHCID 736225(S)-4-Benzyl-2-oxazolidinoneHCID 9822765HCID 9822765, compoundHCID 23665647Potassium tert-butoxide

Product 1

HCID 68847889HCID 68847889, compoundYield 13.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

(±)-2-Ethyl-3-[4-methoxy-3-[[N-[4-(trifluoromethyl)phenyl]carbamoyl]methyl]phenyl]propanoic acid (compound in Example 88: 14.2 g, 34.7 mmol) and dehydrated tetrahydrofuran (100 mL) were mixed under an argon atmosphere, and triethylamine (4.86 ml, 35.0 mmol) and pivaloyl chloride (4.27 mL, 34.7 mmol) were added dropwise under stirring and cooling with ice. Thereafter, the mixture was stirred for 1 hour at room temperature to synthesize mixed acid anhydride. On the other hand, potassium tert-butoxide (4.67 g, 41.6 mmol) and dehydrated tetrahydrofuran (45 mL) were mixed under cooling with ice and argon atmosphere in another vassel, and (S)-4-benzyl-oxazolidine-2-one (7.38 g, 41.6 mmol) dissolved into dehydrated tetrahydrofuran (60 mL) was added dropwise. After completion of the dropwise addition, the mixture was stirred for 30 minutes. Next, a suspension of the mixed acid anhydride synthesized previously was added dropwise while filtering under an atmosphere of argon. After completion of the drop-wise addition, the reaction mixture was concentrated and then poured in water, which was extracted with ethyl acetate. The extracte was washed with 5% hydrochloric acid, saturated aqueous solution of sodium hydrogencarbonate and brine, then dried over anhydrous magnesium sulfate, and concentrated. The residue was purified by means of silica gel column chromatography (eluent: isopropyl ether) to afford 2.65 g (13%) of (4S)-3-[2-ethyl-3-[4-methoxy-3-[[N-[4-(trifluoromethyl)phenyl]carbamoyl]methyl]phenyl]-propanoyl]-4-benzyloxazolidine-2-one with high polarity as a oily product. Also, 3.84 g (20%) of (4S)-3-[2-ethyl-3-[4-methoxy-3-[[N-[4-(trifluoromethyl)phenyl]carbamoyl]-methyl]phenyl]propanoyl]-4-benzyloxazolidine-2-one with low polarity were obtained by purifying by silica gel column chromatography, followed by further recrystallization from a mixed solvent of n-hexane with isopropyl ether, as colorless powder.

Workup

  1. temperaturecooling with ice
  2. stirringThereafter, the mixture was stirred for 1 hour at room temperature
  3. additionwas added dropwise
  4. additionAfter completion of the dropwise addition
  5. stirringthe mixture was stirred for 30 minutes
  6. customsynthesized previously
  7. additionwas added dropwise
  8. filtrationwhile filtering under an atmosphere of argon
  9. additionAfter completion of the drop-wise addition
  10. concentrationthe reaction mixture was concentrated
  11. additionpoured in water
  12. extractionwhich was extracted with ethyl acetate
  13. washThe extracte was washed with 5% hydrochloric acid, saturated aqueous solution of sodium hydrogencarbonate and brine
  14. dry with materialdried over anhydrous magnesium sulfate
  15. concentrationconcentrated
  16. customThe residue was purified by means of silica gel column chromatography (eluent: isopropyl ether)

Sources & evidence

ORD record
ord-f2fc49f9eab844b0bb4c022a5fada8f2
Source dataset
uspto-grants-2006_05
Patent number
US07049342B2

Reaction notes

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