Dicyclohexylcarbodiimide → HCID 58556961, compound

HRID 1044034

Reaction equation

HRID 1044034 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([NH:12][C:13]2[CH:18]=[CH:17][CH:16]=[C:15]([F:19])[CH:14]=2)[C:9]([OH:11])=[O:10])=[CH:4][CH:3]=1.[N:20]12[CH2:27][CH2:26][CH:23]([CH2:24][CH2:25]1)[C@@H:22](O)[CH2:21]2.C1C=CC2N(O)N=NC=2C=1.C1CCC(N=C=NC2CCCCC2)CC1>C1COCC1>[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([NH:12][C:13]2[CH:18]=[CH:17][CH:16]=[C:15]([F:19])[CH:14]=2)[C:9]([O:11][C@@H:22]2[CH:23]3[CH2:26][CH2:27][N:20]([CH2:25][CH2:24]3)[CH2:21]2)=[O:10])=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 10868DicyclohexylcarbodiimideHCID 757711-HydroxybenzotriazoleHCID 914043-Quinuclidinol, (-)-HCID 54890833(4-Fluoro-phenyl)-(3-fluoro-phenylamino)-acetic acid

Product 1

HCID 58556961HCID 58556961, compoundYield 50%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A mixture of 2-(4-fluorophenyl)-2-(3-fluorophenylamino)acetic acid (I3) (510 mg, 1.94 mmol), (R)-quinuclidin-3-ol (246 mg, 1.94 mmol), HOBT (356 mg, 2.32 mmol), and DCC (480 mg, 2.32 mmol) in THF (10 ml) was stirred at room temperature overnight (UPLC-MS monitoring: complete conversion). The solvent was evaporated, the crude was dissolved in EtOAc, and the insoluble was removed by filtration. The clear solution was washed with 1N K2CO3 and then with brine. The organic layer was dried over Na2SO4, filtered and evaporated. The crude product was purified by silica gel chromatography (EtOAc/MeOH=8/2) to give (R)-quinuclidin-3-yl 2-(4-fluorophenyl)-2-(3-fluorophenylamino)acetate (360 mg, 50% yield, mixture of diastereomers).

Workup

  1. customThe solvent was evaporated
  2. dissolutionthe crude was dissolved in EtOAc
  3. customthe insoluble was removed by filtration
  4. washThe clear solution was washed with 1N K2CO3
  5. dry with materialThe organic layer was dried over Na2SO4
  6. filtrationfiltered
  7. customevaporated
  8. customThe crude product was purified by silica gel chromatography (EtOAc/MeOH=8/2)

Sources & evidence

ORD record
ord-8bfe7afcb6cd4d8db3101347a360df3f
Source dataset
uspto-grants-2013_10
Patent number
US08563577B2

Linked notes

Loading…