Water → Biphenyl-2-ylcarbamic acid 1-[2-(4-hydroxymethyl-2,5-dimethylphenylcarbamoyl)ethyl]piperidin-4-yl ester

HRID 1094969Notes

Reaction equation

HRID 1094969 reaction equation
C[O:2][C:3](=O)[C:4]1[CH:9]=[C:8]([CH3:10])[C:7]([NH:11][C:12](=[O:37])[CH2:13][CH2:14][N:15]2[CH2:20][CH2:19][CH:18]([O:21][C:22](=[O:36])[NH:23][C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=3[C:30]3[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=3)[CH2:17][CH2:16]2)=[CH:6][C:5]=1[CH3:38].[H-].[Al+3].[Li+].[H-].[H-].[H-].O.[OH-].[Na+]>O1CCCC1>[OH:2][CH2:3][C:4]1[C:5]([CH3:38])=[CH:6][C:7]([NH:11][C:12]([CH2:13][CH2:14][N:15]2[CH2:16][CH2:17][CH:18]([O:21][C:22](=[O:36])[NH:23][C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=3[C:30]3[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=3)[CH2:19][CH2:20]2)=[O:37])=[C:8]([CH3:10])[CH:9]=1

Participants

6

Reactant 4

HCID 962Water2×HCID 14798Sodium HydroxideHCID 21226445Aluminium lithium hydrideHCID 46239621Methyl 4-{3-[4-(biphenyl-2-ylcarbamoyloxy)piperidin-1-yl]propionylamino}-2,5-dimethylbenzoate

Product 1

HCID 46239523Biphenyl-2-ylcarbamic acid 1-[2-(4-hydroxymethyl-2,5-dimethylphenylcarbamoyl)ethyl]piperidin-4-yl esterYield 52.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 4-{3-[4-(biphenyl-2-ylcarbamoyloxy)piperidin-1-yl]propionylamino}-2,5-dimethylbenzoic acid methyl ester (49.8 g, 93.9 mmol) in tetrahydrofuran (200 mL) was cooled to 0° C. and lithium aluminum hydride (10.7 g, 281.7 mmol) added portion-wise (10×1.07 g). The resulting mixture was stirred for 3 hours and then water (10.7 mL) was added, followed by 1N aqueous sodium hydroxide (10.7 mL) and additional water (32.1 mL). This mixture was stirred overnight and then filtered. The organic layer was concentrated under vacuum and the residue was mixed with ethyl acetate (about 5:1 v/w ethyl acetate to residue). This mixture was heated until all the solid material dissolved and then the solution was allowed to cool to room temperature. The resulting precipitate was filtered and dried to afford biphenyl-2-ylcarbamic acid 1-[2-(4-hydroxymethyl-2,5-dimethylphenylcarbamoyl)ethyl]piperidin-4-yl ester (24.6 g, 95% purity, 47.5% yield). This material was used without further purification. m/z: [M+H+] calcd for C30H35N3O4 502.62; found 502.5.

Workup

  1. stirringThis mixture was stirred overnight
  2. filtrationfiltered
  3. concentrationThe organic layer was concentrated under vacuum
  4. additionthe residue was mixed with ethyl acetate (about 5:1 v/w ethyl acetate to residue)
  5. temperatureThis mixture was heated until all the solid material
  6. dissolutiondissolved
  7. filtrationThe resulting precipitate was filtered
  8. customdried

Sources & evidence

ORD record
ord-1ed8b25cf64449e080f2a58365f0713d
Source dataset
uspto-grants-2012_03
Patent number
US08134006B2

Reaction notes

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