Triethylamine → HCID 67015690, compound

HRID 1888723Notes

Reaction equation

HRID 1888723 reaction equation
[C:1]([O:5][C:6]([NH:8][CH:9]([C:11]([OH:13])=O)[CH3:10])=[O:7])([CH3:4])([CH3:3])[CH3:2].C(N(CC)CC)C.C(Cl)(=O)OCC(C)C.[NH2:29][C:30]1[CH:39]=[CH:38][C:33]([C:34]([O:36][CH3:37])=[O:35])=[CH:32][C:31]=1[S:40][CH2:41][CH2:42][C:43]([O:45][CH2:46][CH:47]([CH2:52][CH3:53])[CH2:48][CH2:49][CH2:50][CH3:51])=[O:44]>C1COCC1.C(OCC)(=O)C>[C:1]([O:5][C:6]([NH:8][C@H:9]([C:11]([NH:29][C:30]1[CH:39]=[CH:38][C:33]([C:34]([O:36][CH3:37])=[O:35])=[CH:32][C:31]=1[S:40][CH2:41][CH2:42][C:43]([O:45][CH2:46][CH:47]([CH2:52][CH3:53])[CH2:48][CH2:49][CH2:50][CH3:51])=[O:44])=[O:13])[CH3:10])=[O:7])([CH3:2])([CH3:3])[CH3:4]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 62365Isobutyl chloroformateHCID 2684712-N-Boc-aminopropionic acidHCID 67015775HCID 67015775, compound

Product 1

HCID 67015690HCID 67015690, compoundYield 37.8%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of N-(tert-butoxycarbonyl)-D,L-alanine (1.70 g, 8.98 mmol) and triethylamine (1.25 mL, 8.98 mmol) in THF (10 mL) was added 2-methylpropyl chlorocarbonate (1.16 mL, 8.98 mmol) under ice-cooling, and the mixture was stirred for 30 min. To this solution was added a solution of methyl 4-amino-3-({3-[(2-ethylhexyl)oxy]-3-oxopropyl}sulfanyl)benzoate (3.00 g, 8.16 mmol) obtained in Reference Example 82 in THF (4 mL) under a nitrogen atmosphere, and the mixture was heated under reflux at 80° C. for 16 hr. After being allowed to cool to room temperature, the reaction mixture was diluted with ethyl acetate, and the mixture was washed with 0.5N hydrochloric acid, 10% aqueous potassium carbonate solution and saturated brine, and dried over anhydrous sodium sulfate. This solution was applied to basic silica gel column chromatography (ethyl acetate). The solvent was evaporated under reduced pressure, and the obtained residue was purified by silica gel column chromatography (hexane:ethyl acetate=19:1 to 7:3) to give methyl 4-{[N-(tert-butoxycarbonyl)alanyl]amino}-3-({3-[(2-ethylhexyl)oxy]-3-oxopropyl}sulfanyl)benzoate (1.66 g). To the obtained oil (1.66 g, 3.08 mmol) was added trifluoroacetic acid (15 mL), and the mixture was stirred for 10 min. The reaction mixture was concentrated under reduced pressure. Ethyl acetate was added to the residue, and the mixture was washed with 10% aqueous potassium carbonate solution and saturated brine, and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure to give methyl 4-(alanylamino)-3-({3-[(2-ethylhexyl)oxy]-3-oxopropyl}sulfanyl)benzoate (1.32 g). To a solution of this oil (1.32 g, 3.01 mmol) in ethyl acetate (15 mL) was added acetic anhydride (0.437 mL, 4.62 mmol) at room temperature and the mixture was stirred for 30 min. The solvent was evaporated under reduced pressure, and the residue was dissolved in ethyl acetate. The solution was purified by basic silica gel column chromatography (ethyl acetate) and the obtained residue was triturated with hexane to give the title compound (1.04 g, yield 70%).

Workup

  1. temperaturecooling
  2. temperaturethe mixture was heated
  3. temperatureto cool to room temperature
  4. washthe mixture was washed with 0.5N hydrochloric acid, 10% aqueous potassium carbonate solution and saturated brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. customThe solvent was evaporated under reduced pressure
  7. customthe obtained residue was purified by silica gel column chromatography (hexane:ethyl acetate=19:1 to 7:3)

Sources & evidence

ORD record
ord-b884baf4673144d6b96298307b8b806b
Source dataset
uspto-grants-2013_08
Patent number
US08501804B2

Reaction notes

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