Dicyclohexylcarbodiimide → (R)-quinuclidin-3-yl 2-(4-fluorophenyl)-2-(3-fluorophenylamino)acetate

HRID 1255044Notes

Reaction equation

HRID 1255044 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>[N:20]12[CH2:27][CH2:26][CH:23]([CH2:24][CH2:25]1)[C@@H:22]([O:10][C:9](=[O:11])[CH:8]([C:5]1[CH:6]=[CH:7][C:2]([F:1])=[CH:3][CH:4]=1)[NH:12][C:13]1[CH:18]=[CH:17][CH:16]=[C:15]([F:19])[CH:14]=1)[CH2:21]2

Participants

6

Reactant 4

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

Product 1

HCID 58556961(R)-quinuclidin-3-yl 2-(4-fluorophenyl)-2-(3-fluorophenylamino)acetateYield 50%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A mixture of (4-fluoro-phenyl)-(3-fluoro-phenylamino)-acetic acid (I83) (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) is stirred at RT overnight (UPLC-MS monitoring: complete conversion). The solvent is evaporated, the crude is dissolved in EtOAc and the insoluble is filtered off The clear solution is washed with 1N K2CO3 and then with brine. The organic layer is dried over Na2SO4, filtered and evaporated. The crude is purified by silica gel chromatography (EtOAc/MeOH=8/2) to give the title compound as a yellow oil (360 mg, 50% yield, mixture of diastereoisomers).

Workup

  1. customThe solvent is evaporated
  2. dissolutionthe crude is dissolved in EtOAc
  3. filtrationthe insoluble is filtered off The clear solution
  4. washis washed with 1N K2CO3
  5. dry with materialThe organic layer is dried over Na2SO4
  6. filtrationfiltered
  7. customevaporated
  8. customThe crude is purified by silica gel chromatography (EtOAc/MeOH=8/2)

Sources & evidence

ORD record
ord-0b13660c2fa3424292dca9e67c2c534c
Source dataset
uspto-grants-2013_06
Patent number
US08455646B2

Reaction notes

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