Dicyclohexylcarbodiimide → HCID 58556901, compound

HRID 453688Notes

Reaction equation

HRID 453688 reaction equation
C1(N=C=NC2CCCCC2)CCCCC1.Cl.[F:17][C:18]1[CH:19]=[C:20]([CH:24]([NH:28][C:29]2[CH:34]=[C:33]([F:35])[C:32]([F:36])=[C:31]([F:37])[CH:30]=2)[C:25]([OH:27])=[O:26])[CH:21]=[CH:22][CH:23]=1.C1C=CC2N(O)N=NC=2C=1.[N:48]12[CH2:55][CH2:54][CH:51]([CH2:52][CH2:53]1)[C@@H:50](O)[CH2:49]2>O1CCCC1>[F:17][C:18]1[CH:19]=[C:20]([CH:24]([NH:28][C:29]2[CH:34]=[C:33]([F:35])[C:32]([F:36])=[C:31]([F:37])[CH:30]=2)[C:25]([O:27][C@@H:50]2[CH:51]3[CH2:54][CH2:55][N:48]([CH2:53][CH2:52]3)[CH2:49]2)=[O:26])[CH:21]=[CH:22][CH:23]=1

Participants

6

Reactant 4

HCID 10868Dicyclohexylcarbodiimide2×HCID 757711-HydroxybenzotriazoleHCID 914043-Quinuclidinol, (-)-HCID 67126860HCID 67126860, compound

Product 1

HCID 58556901HCID 58556901, compoundYield 99.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Polymer-Supported DiCyclohexylCarbodiimide (PS-DCC) (972 mg, 1.29 mmol, loading: 1.33 mmol/g) was suspended in dry tetrahydrofuran (10 ml). 2-(3-fluorophenyl)-2-(3,4,5-trifluorophenylamino)acetic acid hydrochloride (I42) (217 mg, 0.65 mmol), HOBT (198 mg, 1.29 mmol), and (R)-quinuclidin-3-ol (247 mg, 1.94 mmol) were added, and the mixture was shaken at r.t. for 16 hours. PS-DCC was filtered off, the filtrate was evaporated and the residue was dissolved in EtOAc and washed with NaHCO3, water and brine. The organic layer was dried over Na2SO4, filtered and evaporated. The resulting crude compound was purified by filtration through a pad of silica-gel eluting with DCM/MeOH=93/7. The resulting white foam was dissolved in DCM and passed through an Isolute PE-AX cartridge (5 g, 0.6 mmol/g, DCM/MeOH=9/1) to obtain (R)-quinuclidin-3-yl 2-(3-fluorophenyl)-2-(3,4,5-trifluorophenylamino)acetate (264 mg, 32% yield).

Workup

  1. filtrationPS-DCC was filtered off
  2. customthe filtrate was evaporated
  3. dissolutionthe residue was dissolved in EtOAc
  4. washwashed with NaHCO3, water and brine
  5. dry with materialThe organic layer was dried over Na2SO4
  6. filtrationfiltered
  7. customevaporated
  8. filtrationThe resulting crude compound was purified by filtration through a pad of silica-gel
  9. washeluting with DCM/MeOH=93/7
  10. dissolutionThe resulting white foam was dissolved in DCM

Sources & evidence

ORD record
ord-90436256c2614df3ac00aec6bc366fda
Source dataset
uspto-grants-2013_07
Patent number
US08492548B2

Reaction notes

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