Dicyclohexylcarbodiimide → (R)-quinuclidin-3-yl 2-(4-chlorophenylamino)-2-phenylacetate

HRID 76978

Reaction equation

HRID 76978 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][CH:9]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[C:10]([OH:12])=[O:11])=[CH:4][CH:3]=1.C1CCC(N=C=NC2CCCCC2)CC1.C1C=CC2N(O)N=NC=2C=1.[N:44]12[CH2:51][CH2:50][CH:47]([CH2:48][CH2:49]1)[C@@H:46](O)[CH2:45]2>C1COCC1>[N:44]12[CH2:51][CH2:50][CH:47]([CH2:48][CH2:49]1)[C@@H:46]([O:11][C:10](=[O:12])[CH:9]([NH:8][C:5]1[CH:6]=[CH:7][C:2]([Cl:1])=[CH:3][CH:4]=1)[C:13]1[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=1)[CH2:45]2

Participants

6

Reactant 4

HCID 10868DicyclohexylcarbodiimideHCID 757711-HydroxybenzotriazoleHCID 914043-Quinuclidinol, (-)-HCID 305145(4-Chloro-phenylamino)-phenyl-acetic acid

Product 1

HCID 46840420(R)-quinuclidin-3-yl 2-(4-chlorophenylamino)-2-phenylacetateYield 37.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of (4-chloro-phenylamino)-phenyl-acetic acid (I28) (574 mg, 2.20 mmol) in dry THF (20 mL), are added DCC (543 mg, 2.64 mmol), HOBt (359 mg, 2.64 mmol) and 3(R)-quinuclidinol (558 mg, 4.40 mmol). The resulting mixture is stirred at RT overnight (UPLC-MS monitoring: complete conversion). The solvent is evaporated and the residue is portitioned between EtOAc and 2M K2CO3. The organic phase is dried over Na2SO4, filtered and evaporated to dryness. The resulting crude is purified by flash chromatography (DCM/MeOH=99/1 to 85/15) to obtain the title compound as a white solid (306 mg, 37% yield, mixture of diastereoisomers).

Workup

  1. customThe solvent is evaporated
  2. dry with materialThe organic phase is dried over Na2SO4
  3. filtrationfiltered
  4. customevaporated to dryness
  5. customThe resulting crude is purified by flash chromatography (DCM/MeOH=99/1 to 85/15)

Sources & evidence

ORD record
ord-ec2ac91b91924a1c803577c4259fa398
Source dataset
uspto-grants-2014_09
Patent number
US08835682B2

Linked notes

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