Dicyclohexylcarbodiimide → HCID 118135599, compound

HRID 2279941Notes

Reaction equation

HRID 2279941 reaction equation
[CH2:1]([O:8][C:9]([NH:11][CH:12]([C:16]1[CH:21]=[CH:20][CH:19]=[C:18]([O:22][CH2:23][C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[CH:17]=1)[C:13]([OH:15])=[O:14])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C1(N=C=NC2CCCCC2)CCCCC1.O.ON1C2C=CC=CC=2N=N1.[N:56]12[CH2:63][CH2:62][CH:59]([CH2:60][CH2:61]1)[C@@H:58](O)[CH2:57]2>O1CCCC1>[N:56]12[CH2:63][CH2:62][CH:59]([CH2:60][CH2:61]1)[C@@H:58]([O:14][C:13](=[O:15])[CH:12]([NH:11][C:9]([O:8][CH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1)=[O:10])[C:16]1[CH:21]=[CH:20][CH:19]=[C:18]([O:22][CH2:23][C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)[CH:17]=1)[CH2:57]2

Participants

6

Reactant 4

HCID 10868DicyclohexylcarbodiimideHCID 914043-Quinuclidinol, (-)-2×HCID 27960291-Hydroxybenzotriazole hydrateHCID 118116930HCID 118116930, compound

Product 1

HCID 118135599HCID 118135599, compoundYield 56.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of 2-(((benzyloxy)carbonyl)amino)-2-(3-(benzyloxy)phenyl)acetic acid (2.1 g, 5.3 mmol), N,N′-dicyclohexylcarbodiimide (1.20 g, 5.83 mmol), 1-hydroxybenzotriazole hydrate (787 mg, 5.83 mmol) and (R)-quinuclidin-3-ol (1.70 g, 13.5 mmol) in dry tetrahydrofuran (27 mL) was stirred at room temperature for 18 h. Additional (R)-quinuclidin-3-ol (1.70 g, 13.5 mmol) was then added to the mixture and stirred for 4 days. The white slurry was then filtered through a pad of Celite®, rinsed with ethyl acetate (100 mL) and the solvent was removed in vacuo. The residue was partitioned between ethyl acetate (100 mL) and saturated sodium carbonate (50 mL). The layers were separated and the aqueous phase back-extracted with ethyl acetate (2×50 mL). The combined organic fractions were dried over magnesium sulfate, filtered and the solvent was removed in vacuo. The residue was purified by silica gel column chromatography, eluting with 0-40% ethyl acetate/10% methanolic ammonia solution in ethyl acetate to afford the title compound (1.5 g, 56%) as a clear thick oil.

Workup

  1. filtrationThe white slurry was then filtered through a pad of Celite®
  2. washrinsed with ethyl acetate (100 mL)
  3. customthe solvent was removed in vacuo
  4. customThe residue was partitioned between ethyl acetate (100 mL) and saturated sodium carbonate (50 mL)
  5. customThe layers were separated
  6. extractionthe aqueous phase back-extracted with ethyl acetate (2×50 mL)
  7. dry with materialThe combined organic fractions were dried over magnesium sulfate
  8. filtrationfiltered
  9. customthe solvent was removed in vacuo
  10. customThe residue was purified by silica gel column chromatography
  11. washeluting with 0-40% ethyl acetate/10% methanolic ammonia solution in ethyl acetate

Sources & evidence

ORD record
ord-b747cfb147a040c59b77019ef9ed7a84
Source dataset
uspto-grants-2015_09
Patent number
US09133185B2

Reaction notes

Loading…