Ethyl Bromide → Decanoic acid, 10-hydroxy-, ethyl ester

HRID 444678Notes

Reaction equation

HRID 444678 reaction equation
[OH:1][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][C:11]([OH:13])=[O:12].[CH2:14](Br)[CH3:15].C(=O)([O-])[O-].[Li+].[Li+]>CN(C=O)C>[CH2:14]([O:12][C:11](=[O:13])[CH2:10][CH2:9][CH2:8][CH2:7][CH2:6][CH2:5][CH2:4][CH2:3][CH2:2][OH:1])[CH3:15]

Participants

5

Reactant 3

HCID 6332Ethyl BromideHCID 11125Lithium CarbonateHCID 7430010-Hydroxydecanoic Acid

Product 1

HCID 21266885Decanoic acid, 10-hydroxy-, ethyl esterYield 28%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

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.

Workup

  1. extractionThen the product was extracted with ether (30 mL)
  2. washthe ether solution was washed with 1 N NaOH aqueous solution (20 mL) and water (30 mL)
  3. dry with materialdried over Na2SO4
  4. concentrationconcentrated
  5. customThe residue was purified by column chromatography on silica gel eluting with hexane and ethyl acetate (3:1)

Sources & evidence

ORD record
ord-bb51b08245c84391aac7c7617248b2e1
Source dataset
uspto-grants-2013_07
Patent number
US08476043B2

Reaction notes

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