Ethyl Acetate → HCID 10183718, compound

HRID 1935199Notes

Reaction equation

HRID 1935199 reaction equation
C([O:3][C:4](=O)[CH2:5][C:6]1[N:7]=[C:8]([NH:11][C:12](=[O:36])[CH:13]([C:20]2[CH:25]=[CH:24][C:23]([C:26]3[C:35]4[C:30](=[CH:31][CH:32]=[CH:33][CH:34]=4)[CH:29]=[CH:28][CH:27]=3)=[CH:22][CH:21]=2)[CH2:14][CH:15]2[CH2:19][CH2:18][CH2:17][CH2:16]2)[S:9][CH:10]=1)C.[H-].[Al+3].[Li+].[H-].[H-].[H-].C(OCC)(=O)C>C(OCC)C>[CH:15]1([CH2:14][CH:13]([C:20]2[CH:21]=[CH:22][C:23]([C:26]3[C:35]4[C:30](=[CH:31][CH:32]=[CH:33][CH:34]=4)[CH:29]=[CH:28][CH:27]=3)=[CH:24][CH:25]=2)[C:12]([NH:11][C:8]2[S:9][CH:10]=[C:6]([CH2:5][CH2:4][OH:3])[N:7]=2)=[O:36])[CH2:19][CH2:18][CH2:17][CH2:16]1

Participants

5

Reactant 3

HCID 8857Ethyl AcetateHCID 10164611HCID 10164611, compoundHCID 21226445Aluminium lithium hydride

Product 1

HCID 10183718HCID 10183718, compoundYield 34.5%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent

Conditions

Temperature
0 °C

Procedure

A solution of {2-[3-cyclopentyl-2-(4-naphthalen-1-yl-phenyl)-propionylamino]-thiazol-4-yl}-acetic acid ethyl ester (prepared in Example 5B-b, 60 mg, 0.117 mmol) in diethyl ether (1 mL) was cooled to 0° C. and then slowly treated with lithium aluminum hydride powder (6.7 mg, 0.176 mmol). The reaction mixture was stirred at 0° C. for 30 min, at which time, thin layer chromatography showed the absence of starting material. The reaction mixture was slowly quenched by the dropwise addition of a saturated aqueous sodium bicarbonate solution (2 mL). The resulting reaction mixture was treated with ethyl acetate (2 mL) and allowed to stir at 25° C. for 15 h. The two-phase reaction mixture was then partitioned between water (20 mL) and ethyl acetate (20 mL), and the layers were separated. The aqueous layer was further extracted with ethyl acetate (1×20 mL). The combined organic extracts were dried over magnesium sulfate, filtered, and concentrated in vacuo. Flash chromatography (Merck Silica gel 60, 230-400 mesh, 1/2 hexanes/ethyl acetate) afforded 3-cyclopentyl-N-[4-(2-hydroxyethyl)-thiazol-2-yl]-2-(4-naphthalen-1-yl-phenyl)-propionamide (19 mg, 34%) as a yellow foam: mp 84-87° C.; EI-HRMS m/e calcd for C29H30N2O2S (M+) 470.2028, found 470.2020.

Workup

  1. customThe reaction mixture was slowly quenched by the dropwise addition of a saturated aqueous sodium bicarbonate solution (2 mL)
  2. customThe resulting reaction mixture
  3. stirringto stir at 25° C. for 15 h
  4. customThe two-phase reaction mixture
  5. customwas then partitioned between water (20 mL) and ethyl acetate (20 mL)
  6. customthe layers were separated
  7. extractionThe aqueous layer was further extracted with ethyl acetate (1×20 mL)
  8. dry with materialThe combined organic extracts were dried over magnesium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-5513660cb199402ea4f9ab0865e1e420
Source dataset
uspto-grants-2002_05
Patent number
US06384220B2

Reaction notes

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