تفاعل #531860

ord-bb51b08245c84391aac7c7617248b2e1

معادلة التفاعل

O=C(O)CCCCCCCCCO
10-hydroxydecanoic acid
CCBr
ethyl bromide
O=C([O-])[O-].[Li+].[Li+]
lithium carbonate
CCOC(=O)CCCCCCCCCO
10-hydroxydecanoic acid ethyl ester
المردود 28.0%

المذيبات

ظروف التفاعل

الظروف التفصيلية
See reaction.notes.procedure_details.

المعالجة

  1. 1
    استخلاصThen the product was extracted with ether (30 mL)
  2. 2
    غسيلthe ether solution was washed with 1 N NaOH aqueous solution (20 mL) and water (30 mL)
  3. 3
    تجفيفdried over Na2SO4
  4. 4
    تركيزconcentrated
  5. 5
    أخرىThe residue was purified by column chromatography on silica gel eluting with hexane and ethyl acetate (3:1)

الإجراء التجريبي

A mixture of 10-hydroxydecanoic acid (0.25 g, 1.33 mmol; 11-hydroxyundecanoic acid for compound 881 and 12-hydroxydodecanoic acid for compound 882), ethyl bromide (0.16 g, 1.46 mmol), and lithium carbonate (0.11 g, 1.46 mmol) in DMF (25 mL) was stirred at 70 C for 6 h. Then the 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 with hexane and ethyl acetate (3:1) to give 10-hydroxydecanoic acid ethyl ester (80 mg, 28%). This alcohol was coupled with 4-(3-adamantan-1-yl-ureido)butyric acid 822 by using EDCI/DMAP coupling reagent to give 880 (0.11 g, 60%) as a solid: 1H NMR (CDCl3) 1.24-1.32 (13H, m), 1.62-1.68 (10H, m), 1.80 (2H, quint, J=6.9 Hz), 1.94-1.97 (6H, m), 2.05-2.07 (3H, m), 2.28 (2H, t, J=6.9 Hz), 2.36 (2H, t, J=6.9 Hz), 3.16 (2H, q, J=6.9 Hz), 4.05-4.14 (5H, m), 4.25 (1H, s); LC-MS (ESI) m/z calcd for C27H46N2O5 [M+H]+ 479.34. found [M+H]+ 479.29; mp 60-61 C. Anal. Calcd for C27H46N2O5: C, 67.75; H, 9.69; N, 5.85. Found: C, 68.33; H, 9.92; N, 5.97.

المصدر

DOI: 10.6084/m9.figshare.5104873.v1براءة الاختراع: US08476043B2uspto-grants-2013_07