{4-[4-(2-{Benzyl-[2-(4-benzyloxy-3-formylaminophenyl)-2-(R)-hydroxyethyl]amino}-ethoxy)phenyl]butyl}carbamic acid benzyl ester → N-[5-(2-{2-[4-(4-Aminobutyl)phenoxy]ethylamino}-1-(R)-hydroxyethyl)-2-hydroxyphenyl]formamide

HRID 1696832Notes

Reaction equation

HRID 1696832 reaction equation
C(OC(=O)[NH:10][CH2:11][CH2:12][CH2:13][CH2:14][C:15]1[CH:20]=[CH:19][C:18]([O:21][CH2:22][CH2:23][N:24](CC2C=CC=CC=2)[CH2:25][C@@H:26]([C:28]2[CH:33]=[CH:32][C:31]([O:34]CC3C=CC=CC=3)=[C:30]([NH:42][CH:43]=[O:44])[CH:29]=2)[OH:27])=[CH:17][CH:16]=1)C1C=CC=CC=1>C(O)C.[OH-].[OH-].[Pd+2]>[NH2:10][CH2:11][CH2:12][CH2:13][CH2:14][C:15]1[CH:20]=[CH:19][C:18]([O:21][CH2:22][CH2:23][NH:24][CH2:25][C@@H:26]([C:28]2[CH:33]=[CH:32][C:31]([OH:34])=[C:30]([NH:42][CH:43]=[O:44])[CH:29]=2)[OH:27])=[CH:17][CH:16]=1

Participants

4

Reactant 1

HCID 58100114{4-[4-(2-{Benzyl-[2-(4-benzyloxy-3-formylaminophenyl)-2-(R)-hydroxyethyl]amino}-ethoxy)phenyl]butyl}carbamic acid benzyl ester

Product 1

HCID 58100124N-[5-(2-{2-[4-(4-Aminobutyl)phenoxy]ethylamino}-1-(R)-hydroxyethyl)-2-hydroxyphenyl]formamideYield 53.1%

Reagents, catalysts & solvents 2

HCID 9942167Palladium hydroxideCatalystHCID 702EthanolSolvent

Procedure

α-Aminoalcohol 17 (500 mg, 0.71 mmol) was dissolved in ethanol (20 mL). Following the standard hydrogenation procedure, palladium dihydroxide (20% on carbon, 50% wet) was added. The reaction mixture was stirred for 15 h at ambient temperature under atmospheric H2 pressure. The catalyst was removed by filtration through diatomaceous earth and the filtrate was concentrated to a yellow solid. Purification of the crude solid by column chromatography eluting with 10-30% (20% concentrated ammonium hydroxide in methanol) in dichloromethane gave 18 (146 mg, 53%) as a yellow solid: 1H NMR (300 MHz, CD3OD) δ 1.29-1.72 (m, 5H), 1.93 (s, 3H), 2.58 (t, 2H), 2.71-2.90 (m, 4H), 2.99 (t, 2H), 4.05 (t, 2H), 4.66-4.72 (m, 1H), 6.78-6.85 (m, 3H), 6.97-7.16 (m, 3H), 7.82-8.04 (m, 1H), 8.29 (s, 1H).

Workup

  1. additionwas added
  2. customThe catalyst was removed by filtration through diatomaceous earth
  3. concentrationthe filtrate was concentrated to a yellow solid
  4. customPurification of the crude solid by column chromatography
  5. washeluting with 10-30% (20% concentrated ammonium hydroxide in methanol) in dichloromethane

Sources & evidence

ORD record
ord-12e561f2aba2408ea05eb0e01838d643
Source dataset
uspto-grants-2012_04
Patent number
US08163758B2

Reaction notes

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