(3R)-1-azabicyclo[2.2.2]octan-3-yl carbonochloridate hydrochloride → Methyl 4-[[3-[(N-[(3R)-quinuclidin-3-yl]oxycarbonylanilino)methyl]-phenoxy]methyl]benzoate

HRID 520335Notes

Reaction equation

HRID 520335 reaction equation
[NH:1]([CH2:8][C:9]1[CH:10]=[C:11]([CH:24]=[CH:25][CH:26]=1)[O:12][CH2:13][C:14]1[CH:23]=[CH:22][C:17]([C:18]([O:20][CH3:21])=[O:19])=[CH:16][CH:15]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl.[C:28](Cl)(=[O:38])[O:29][C@@H:30]1[CH:35]2[CH2:36][CH2:37][N:32]([CH2:33][CH2:34]2)[CH2:31]1>CC#N.CCOC(C)=O>[N:32]12[CH2:37][CH2:36][CH:35]([CH2:34][CH2:33]1)[C@@H:30]([O:29][C:28]([N:1]([CH2:8][C:9]1[CH:10]=[C:11]([CH:24]=[CH:25][CH:26]=1)[O:12][CH2:13][C:14]1[CH:15]=[CH:16][C:17]([C:18]([O:20][CH3:21])=[O:19])=[CH:22][CH:23]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1)=[O:38])[CH2:31]2

Participants

5

Reactant 2

HCID 86676896(3R)-1-azabicyclo[2.2.2]octan-3-yl carbonochloridate hydrochlorideHCID 86720705Methyl 4-((3-((phenylamino)methyl)phenoxy)methyl)benzoate

Product 1

HCID 118558468Methyl 4-[[3-[(N-[(3R)-quinuclidin-3-yl]oxycarbonylanilino)methyl]-phenoxy]methyl]benzoateYield 76%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolvent

Procedure

A suspension of methyl 4-[[3-(anilinomethyl)phenoxy]methyl]benzoate (380 mg, 1.1 mmol) and (R)-quinuclidin-3-yl carbonochloridate hydrochloride (described in the co-pending International Patent Application No. PCT/EP2013/075529 (published as WO 2014/086855) as Intermediate 16) (300 mg, 1.33 mmol) in anhydrous CH3CN (5 mL) was heated to 100° C. for 15 min under microwave irradiation. After cooling to room temperature, the mixture was diluted with EtOAc (50 mL) and washed with saturated aqueous NaHCO3 (20 mL) The layers were separated and the organic phase was dried over Na2SO4, filtered and the solvent was removed in vacuo to yield the title compound (419 mg, 76% yield) which was used directly in the next step without any further purification.

Workup

  1. washwashed with saturated aqueous NaHCO3 (20 mL) The layers
  2. customwere separated
  3. dry with materialthe organic phase was dried over Na2SO4
  4. filtrationfiltered
  5. customthe solvent was removed in vacuo

Sources & evidence

ORD record
ord-eeacebcd412a4541ac52e5693175a1af
Source dataset
uspto-grants-2016_05
Patent number
US09326976B2

Reaction notes

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