4-Hydroxybenzaldehyde → Biphenyl-2-ylcarbamic Acid 1-[2-({3-[2-(4-Hydroxybenzylamino)ethylcarbamoyl]benzoyl}methylamino)ethyl]piperidin-4-yl Ester

HRID 1443310Notes

Reaction equation

HRID 1443310 reaction equation
[NH2:1][CH2:2][CH2:3][NH:4][C:5]([C:7]1[CH:8]=[C:9]([CH:38]=[CH:39][CH:40]=1)[C:10]([CH2:12][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)=[O:11])=[O:6].[OH:41][C:42]1[CH:49]=[CH:48][C:45]([CH:46]=O)=[CH:44][CH:43]=1.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>CO>[OH:41][C:42]1[CH:49]=[CH:48][C:45]([CH2:46][NH:1][CH2:2][CH2:3][NH:4][C:5]([C:7]2[CH:8]=[C:9]([CH:38]=[CH:39][CH:40]=2)[C:10]([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:11])=[O:6])=[CH:44][CH:43]=1

Participants

5

Reactant 3

HCID 1264-HydroxybenzaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 66637371HCID 66637371, compound

Product 1

HCID 66637925Biphenyl-2-ylcarbamic Acid 1-[2-({3-[2-(4-Hydroxybenzylamino)ethylcarbamoyl]benzoyl}methylamino)ethyl]piperidin-4-yl Ester

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A solution of biphenyl-2-ylcarbamic acid 1-(2-{[3-(2-aminoethylcarbamoyl)benzoyl]methylamino}ethyl)piperidin-4-yl ester (9.31 g, 17.1 mmol; prepared as described in Preparation 8) and 4-hydroxybenzaldehyde (2.30 g, 18.8 mmol, 1.1 eq) in 125 mL MeOH was stirred at room temperature for 2 hours. Na(OAc)3BH (7.26 g, 34.2 mmol, 2.0 eq) was added to the reaction at room temperature in two portions separated in one hour interval. The reaction was stirred for an additional hour before being concentrated under vacuum. The residue was taken up in 100 mL DCM and stirred with 100 mL of 1.0 N HCl for 1 hour. The aqueous phase was adjusted to pH 9 using 10.0 N NaOH. The mixture was stirred for an additional 10 minutes. The organic phase was separated, dried over Na2SO4, filtered and concentrated under vacuum. The crude material was purified using silica gel chromatography (7% MeOH in CH2Cl2 with 1% NH4OH as eluent). The title compound was obtained as an off-white solid (8.08 g, 73%). MS m/z: [M+H+] calcd for C38H43N5O5, 650.34. found, 650.2.

Workup

  1. customseparated in one hour interval
  2. concentrationbefore being concentrated under vacuum
  3. stirringstirred with 100 mL of 1.0 N HCl for 1 hour
  4. stirringThe mixture was stirred for an additional 10 minutes
  5. customThe organic phase was separated
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated under vacuum
  9. customThe crude material was purified

Sources & evidence

ORD record
ord-838c6d18334d4ad88980a9467edbb508
Source dataset
uspto-grants-2010_02
Patent number
US07659403B2

Reaction notes

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