Dicyclohexylcarbodiimide → HCID 86603903, compound

HRID 1808656Notes

Reaction equation

HRID 1808656 reaction equation
[OH:1][N:2]=[C:3]([O:5][CH2:6][CH3:7])[CH3:4].Br[CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][C:16]([OH:18])=[O:17].[OH-].[Na+].O[N:22]1[C:26](=[O:27])[CH2:25][CH2:24][C:23]1=[O:28].C1CCC(N=C=NC2CCCCC2)CC1>C1COCC1.CO>[O:28]=[C:23]1[CH2:24][CH2:25][C:26](=[O:27])[N:22]1[O:18][C:16](=[O:17])[CH2:15][CH2:14][CH2:13][CH2:12][CH2:11][CH2:10][CH2:9][O:1][N:2]=[C:3]([O:5][CH2:6][CH3:7])[CH3:4]

Participants

8

Reactant 5

HCID 10868DicyclohexylcarbodiimideHCID 14798Sodium HydroxideHCID 80170N-HydroxysuccinimideHCID 99894Ethyl acetohydroximate2×HCID 5482758-Bromooctanoic acid

Product 1

HCID 86603903HCID 86603903, compoundYield 34%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
50 °C

Procedure

To a mixture of ethyl N-hydroxyacetimidate 1 (6.2 g, 60 mmol) and 8-bromooctanoic acid (15 g, 67 mmol) in 150 mL of solvent mixture (methanol 8:acetone 1) was added drop wise 22 mL of 10N NaOH and heated at 50° C. for 12 h. The reaction mixture was cooled, the organic solvent was removed by rotary evaporation. The dilute HCl solution was added to adjust pH down to 6. The resulting turbid mixture was extracted with CHCl3 and EtOAc. The extract was washed with brine, dried, filtered, and solvent was evaporated to crude oil (3, 12 g, 49 mmol, 82%). A mixture of 3 (12 g, 49 mmol) and N-hydroxysuccinimide (5 g, 50 mmol) in 100 mL of THF was treated with 50 mL of DCC (1.0M solution in CH2Cl2). The solids were filtered, and the clear filtrate was evaporated. The resultant brown oil was purified on a silica gel column. Elution with 20% ethyl acetate/hexane afforded 5.8 g (17 mmol, 34%) of the product as a wet solid. 1H NMR (DMSO-d6): δ 1.21 (3H, t, J=7.0), 1.28-1.38 (6H, m), 1.57 (2H, p, J=6.8), 1.64 (2H, p, J=7.4), 1.86 (3H, s), 2.65 (2H, t, J=7.5), 2.81 (4H, s), 3.82 (2H, t, J=6.5), 3.94 (2H, q, J=7.0)

Workup

  1. temperatureThe reaction mixture was cooled
  2. customthe organic solvent was removed by rotary evaporation
  3. additionThe dilute HCl solution was added
  4. extractionThe resulting turbid mixture was extracted with CHCl3 and EtOAc
  5. washThe extract was washed with brine
  6. customdried
  7. filtrationfiltered
  8. customsolvent was evaporated to crude oil (3, 12 g, 49 mmol, 82%)
  9. filtrationThe solids were filtered
  10. customthe clear filtrate was evaporated
  11. customThe resultant brown oil was purified on a silica gel column
  12. washElution with 20% ethyl acetate/hexane

Sources & evidence

ORD record
ord-856dea325a954c25a728ddc45c1ef343
Source dataset
uspto-grants-2013_01
Patent number
US08361442B2

Reaction notes

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