Reaction #531863

Reaction equation

4-(3-adamantan-1-yl-ureido)butyric acid

4-hydroxyphenylacetic acid

EDCI

bromoethane

K2CO3

→

852

Yield 20.0%

4-(3-Adamantan-1-yl-ureido)butyric Acid 4-Ethoxycarbonylmethylphenyl Ester

Yield 20.0%

Solvents

methylene chloride

DMF

Conditions

Workup

1. 1
   Washthe reaction mixture was washed with water (20 mL)
2. 2
   workup.DISSOLUTIONthe methylene chloride solution dissolving the product
3. 3
   Dryingwas dried over Na2SO4
4. 4
   Concentrationconcentrated
5. 5
   Otherto give
6. 6
   workup.STIRRINGstirred for 12 h at room temperature
7. 7
   ExtractionThe ethyl ester product was extracted with ether (30 mL)
8. 8
   Washthe ether solution was washed with 1 N NaOH aqueous solution (20 mL) and water (30 mL)
9. 9
   Dryingdried over Na2SO4
10. 10
    Concentrationconcentrated
11. 11
    OtherThe residue was purified by column chromatography on silica gel
12. 12
    Washeluting hexane and ethyl acetate (5:1)

Procedure

To a solution of 4-(3-adamantan-1-yl-ureido)butyric acid 822 (0.15 g, 0.54 mmol), DMAP (0.07 g, 0.54 mmol), and 4-hydroxyphenylacetic acid (0.09 g, 0.59 mmol) in methylene chloride (20 mL) was added EDCI (0.11 g, 0.59 mmol) at room temperature. After stirring for 12 h, the reaction mixture was washed with water (20 mL), and the methylene chloride solution dissolving the product was dried over Na2SO4 and concentrated to give conjugated product. This crude mixture in DMF (30 mL) was treated with bromoethane (0.15 g, 1.34 mmol) and K2CO3 (0.18 g, 1.34 mmol) at room temperature and stirred for 12 h at room temperature. The ethyl ester product was extracted with ether (30 mL), and the ether solution was washed with 1 N NaOH aqueous solution (20 mL) and water (30 mL), dried over Na2SO4, and concentrated. The residue was purified by column chromatography on silica gel eluting hexane and ethyl acetate (5:1) to give 852 (47 mg, 20%) as a white solid: 1H NMR (CDCl3) 1.40 (3H, t, J=6.9 Hz), 1.66-1.68 (6H, m), 1.89-1.95 (8H, m), 2.05-2.07 (3H, m), 2.62 (2H, t, J=6.9 Hz), 3.25 (2H, q, J=6.9 Hz), 3.60 (2H, s), 4.07 (1H, s), 4.16 (2H, q, J=6.9 Hz), 4.29 (1H, s), 7.08-7.10 (2H, m), 7.28-7.30 (2H, m); LC-MS (ESI) m/z calcd for C25H34N2O5 [M+H]+ 443.25. found [M+H]+ 443.25; mp 95-97 C. Anal. (C25H34N2O5) C, H, N.

Source