4-Formylbenzoic acid → Biphenyl-2-ylcarbamic Acid 1-{2-[(4-Formylbenzoyl)methylamino]ethyl}piperidin-4-yl Ester

HRID 575862Notes

Reaction equation

HRID 575862 reaction equation
[C:1]([C:4]1[CH:11]=[CH:10][C:7]([CH:8]=[O:9])=[CH:6][CH:5]=1)([OH:3])=O.[CH3:12][NH:13][CH2:14][CH2:15][N:16]1[CH2:21][CH2:20][CH:19]([O:22][C:23](=[O:37])[NH:24][C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=2[C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=2)[CH2:18][CH2:17]1.[Cl-].COC1N=C(OC)N=C([N+]2(C)CCOCC2)N=1>CC1OCCC1>[CH:8]([C:7]1[CH:10]=[CH:11][C:4]([C:1]([CH2:12][NH:13][CH2:14][CH2:15][N:16]2[CH2:21][CH2:20][CH:19]([O:22][C:23](=[O:37])[NH:24][C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=3[C:31]3[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=3)[CH2:18][CH2:17]2)=[O:3])=[CH:5][CH:6]=1)=[O:9]

Participants

5

Reactant 3

HCID 120884-Formylbenzoic acidHCID 27340594-(4,6-Dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chlorideHCID 566436031-(2-(Methylamino)ethyl)piperidin-4-yl [1,1'-biphenyl]-2-ylcarbamate

Product 1

HCID 57436143Biphenyl-2-ylcarbamic Acid 1-{2-[(4-Formylbenzoyl)methylamino]ethyl}piperidin-4-yl Ester

Reagents, catalysts & solvents 1

HCID 73012-MethyltetrahydrofuranSolvent2×

Procedure

4-Carboxybenzaldehyde (9 g, 60 mmol, 1.0 eq.) and biphenyl-2-yl-carbamic acid 1-(2-methylaminoethyl)piperidin-4-yl ester (21.2 g, 60 mmol, 1.0 eq.) were combined in MeTHF (115 mL). The mixture was stirred for 0.5 hours, forming a thick slurry. Additional MeTHF (50 mL) was added to form a free-flowing slurry. 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride (18 g, 63 mmol, 1.1 eq., 97% pure) was added in two portions and the funnel rinsed with additional MeTHF (50 mL). The mixture was stirred at room temperature overnight. MeCN (50 mL) was added and the mixture was filtered. The solids were washed with MeTHF (30 mL). The filtrate and washes were combined and a saturated NaHCO3 solution (100 mL) was added and stirred for 10 minutes. The layers were separated and a saturated NaCl solution (100 mL) was added and stirred for 10 minutes. The layers were separated and the aqueous layer discarded. The resulting solution was concentrated under reduced pressure and held at room temperature for three days, then used directly in the next step.

Workup

  1. customforming a thick slurry
  2. customto form a free-flowing slurry
  3. washthe funnel rinsed with additional MeTHF (50 mL)
  4. stirringThe mixture was stirred at room temperature overnight
  5. additionMeCN (50 mL) was added
  6. filtrationthe mixture was filtered
  7. washThe solids were washed with MeTHF (30 mL)
  8. additiona saturated NaHCO3 solution (100 mL) was added
  9. stirringstirred for 10 minutes
  10. customThe layers were separated
  11. additiona saturated NaCl solution (100 mL) was added
  12. stirringstirred for 10 minutes
  13. customThe layers were separated
  14. concentrationThe resulting solution was concentrated under reduced pressure
  15. waitheld at room temperature for three days

Sources & evidence

ORD record
ord-107040a2d9f749e28a9ccf15afce66ad
Source dataset
uspto-grants-2015_05
Patent number
US09035061B2

Reaction notes

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