Dicyclohexylcarbodiimide → HCID 59401154, compound

HRID 77017Notes

Reaction equation

HRID 77017 reaction equation
Cl.[CH3:2][O:3][C:4]1[CH:9]=[CH:8][C:7]([CH:10]([NH:14][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[C:11]([OH:13])=[O:12])=[CH:6][CH:5]=1.C1CCC(N=C=NC2CCCCC2)CC1.C1C=CC2N(O)N=NC=2C=1.CCN(C(C)C)C(C)C.[N:55]12[CH2:62][CH2:61][CH:58]([CH2:59][CH2:60]1)[C@@H:57](O)[CH2:56]2>C1COCC1>[N:55]12[CH2:62][CH2:61][CH:58]([CH2:59][CH2:60]1)[C@@H:57]([O:12][C:11](=[O:13])[CH:10]([C:7]1[CH:6]=[CH:5][C:4]([O:3][CH3:2])=[CH:9][CH:8]=1)[NH:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)[CH2:56]2

Participants

7

Reactant 5

HCID 10868Dicyclohexylcarbodiimide2×HCID 757711-Hydroxybenzotriazole2×HCID 81531Diisopropylethylamine2×HCID 914043-Quinuclidinol, (-)-2×HCID 67424973(4-Methoxy-phenyl)-phenylamino-acetic acid hydrochloride

Product 1

HCID 59401154HCID 59401154, compoundYield 24.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

(4-Methoxy-phenyl)-phenylamino-acetic acid hydrochloride (I92) (300 mg, 1.02 mmol), DCC (253 mg, 1.23 mmol), and HOBT (188 mg, 1.23 mmol) are dissolved in THF (10 mL). DIPEA (0.36 mL, 2.04 mmol) and (R)-quinuclidin-3-ol (130 mg, 1.02 mmol) are added. The mixture is stirred ad RT for 16 hours. Then DCC (25.3 mg, 0.12 mmol), HOBT (18.8 mg, 0.12 mmol), DIPEA (36 uL, 0.204 mmol) and (R)-quinuclidin-3-ol (13.0 mg, 0.10 mmol) are added again and reaction is stirred for additional 32 hours. THF is evaporated and the residue is dissolved in EtOAc and washed with sat. NaHCO3, H2O and brine. The organic layer is dried (Na2SO4), filtered and evaporated. The crude residue is purified by flash chromatography (DCM/MeOH=97/3 to 92/8) to obtain the title compound as a yellow solid (90 mg, 24% yield, mixture of diastereoisomers).

Workup

  1. customreaction
  2. stirringis stirred for additional 32 hours
  3. customTHF is evaporated
  4. dissolutionthe residue is dissolved in EtOAc
  5. washwashed with sat. NaHCO3, H2O and brine
  6. dry with materialThe organic layer is dried (Na2SO4)
  7. filtrationfiltered
  8. customevaporated
  9. customThe crude residue is purified by flash chromatography (DCM/MeOH=97/3 to 92/8)

Sources & evidence

ORD record
ord-9b48371edf74414fbcd78839e68cc2dd
Source dataset
uspto-grants-2014_09
Patent number
US08835682B2

Reaction notes

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