Dicyclohexylcarbodiimide → (2-methoxy-phenylamino)-phenyl-acetic acid (R)-(1-aza-bicyclo[2.2.2]oct-3-yl)ester

HRID 1255015

Reaction equation

HRID 1255015 reaction equation
C1CCC(N=C=NC2CCCCC2)CC1.Cl.[CH3:17][O:18][C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=1[NH:25][CH:26]([C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1)[C:27]([OH:29])=[O:28].C1C=CC2N(O)N=NC=2C=1.[N:46]12[CH2:53][CH2:52][CH:49]([CH2:50][CH2:51]1)[C@@H:48](O)[CH2:47]2>C1COCC1>[N:46]12[CH2:53][CH2:52][CH:49]([CH2:50][CH2:51]1)[C@@H:48]([O:28][C:27](=[O:29])[CH:26]([NH:25][C:20]1[CH:21]=[CH:22][CH:23]=[CH:24][C:19]=1[O:18][CH3:17])[C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1)[CH2:47]2

Participants

6

Reactant 4

HCID 10868DicyclohexylcarbodiimideHCID 757711-HydroxybenzotriazoleHCID 914043-Quinuclidinol, (-)-HCID 67425641(2-Methoxy-phenylamino)-phenyl-acetic acid hydrochloride

Product 1

HCID 46840572(2-methoxy-phenylamino)-phenyl-acetic acid (R)-(1-aza-bicyclo[2.2.2]oct-3-yl)esterYield 116.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

PS-DCC (2.05 g, 2.57 mmol, loading: 1.25 mmol/g) is suspended in THF (15 mL) and shaken for few minutes. Then (2-methoxy-phenylamino)-phenyl-acetic acid hydrochloride (I36) (377 mg, 1.28 mmol) and HOBT (393 mg, 2.57 mmol) are added. After 10 minutes, (R)-quinuclidin-3-ol (490 mg, 3.85 mmol) is added and the mixture is shaken at RT for 16 hours (Conversion complete by UPLC/MS-UV). PS-DCC is filtered off and the filtrate is evaporated to dryness. The residue is dissolved in EtOAc and washed with sat. NaHCO3, water and brine. The organic layer is recovered, dried over Na2SO4, filtered and evaporated to afford the title compound as a yellow oil (548 mg, quantitative yield, mixture of diastereoisomers).

Workup

  1. stirringthe mixture is shaken at RT for 16 hours (Conversion complete by UPLC/MS-UV)
  2. filtrationPS-DCC is filtered off
  3. customthe filtrate is evaporated to dryness
  4. dissolutionThe residue is dissolved in EtOAc
  5. washwashed with sat. NaHCO3, water and brine
  6. customThe organic layer is recovered
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. customevaporated

Sources & evidence

ORD record
ord-608c20ced0f94d57904956e6697d3256
Source dataset
uspto-grants-2013_06
Patent number
US08455646B2

Linked notes

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