Ethanol → N-[5-(2-{4-[4-(4-Aminobutyl)phenyl]-1-methylbutylamino}-1-(R)-hydroxyethyl)-2-hydroxyphenyl]formamide

HRID 1696837Notes

Reaction equation

HRID 1696837 reaction equation
C(OC(=O)[NH:10][CH2:11][CH2:12][CH2:13][CH2:14][C:15]1[CH:20]=[CH:19][C:18]([CH2:21][CH2:22][CH2:23][CH:24]([NH:26][CH2:27][C@@H:28]([C:30]2[CH:35]=[CH:34][C:33]([O:36]CC3C=CC=CC=3)=[C:32]([NH:44][CH:45]=[O:46])[CH:31]=2)[OH:29])[CH3:25])=[CH:17][CH:16]=1)C1C=CC=CC=1.C(O)C>[Pd].CO>[NH2:10][CH2:11][CH2:12][CH2:13][CH2:14][C:15]1[CH:16]=[CH:17][C:18]([CH2:21][CH2:22][CH2:23][CH:24]([NH:26][CH2:27][C@@H:28]([C:30]2[CH:35]=[CH:34][C:33]([OH:36])=[C:32]([NH:44][CH:45]=[O:46])[CH:31]=2)[OH:29])[CH3:25])=[CH:19][CH:20]=1

Participants

5

Reactant 2

HCID 702EthanolHCID 86649686[4-(4-{4-[2-(4-Benzyloxy-3-formylaminophenyl)-2-(R)-hydroxyethylamino]pentyl}-phenyl)butyl]carbamic acid benzyl ester

Product 1

HCID 86649687N-[5-(2-{4-[4-(4-Aminobutyl)phenyl]-1-methylbutylamino}-1-(R)-hydroxyethyl)-2-hydroxyphenyl]formamideYield 54%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 887MethanolSolvent

Procedure

A mixture of compounds 27 (029 g, 0.45 mmol), palladium catalyst (0.2 g, 10% Pd on carbon, 50% wet), ethanol (10 mL) and methanol (5 mL) underwent hydrogenation at room temperature for 4 h under one H2 pressure. The catalyst was vacuum filtered and washed with ethanol (3×5 mL). The filtrate and the washings were combined and concentrated. The residue was subjected to column chromatography, eluting with a mixture of methanol (0-22%), concentrated ammonium hydroxide (0-2.2%) and dichloromethane (100-75.6%), to afford the desired product 28 (0.10 g, 54%) as a colorless, glass solid: 1H NMR (300 MHz, CD3OD) δ 1.08 (d, 3H), 1.32 (m, 2H), 1.48-1.78 (m, 6H), 2.59 (m, 4H), 2.78 (m, 5H), 3.44 (m, 2H), 4.75 (m, 1H), 6.82 (m, 1H), 7.00 (m, 1H), 7.08 (m, 5H), 8.06 (s, 1H), 8.31 (s, 1H); m/z (ESI) 414 [C31H41N3O3+H]+. The diastereoisomer 29 (13 mg, 7%) was also isolated as a light yellow solid: 1H NMR (300 MHz, CD3OD) δ 1.26 (d, 3H), 1.48-1.90 (m, 8H), 2.50 (m, 4H), 2.82-3.08 (m, 3H), 3.50 (m, 2H), 4.60 (m, 1H), 6.82-6.82 (m, 2H), 7.10 (m, 5H), 8.00 (s, 1H), 8.28 (s, 1H); m/z (ESI) 414 [C31H41N3O3+H]+.

Workup

  1. filtrationfiltered
  2. washwashed with ethanol (3×5 mL)
  3. concentrationconcentrated
  4. washeluting with a mixture of methanol (0-22%), concentrated ammonium hydroxide (0-2.2%) and dichloromethane (100-75.6%)

Sources & evidence

ORD record
ord-553594c6679d493793f0bd353613ac0f
Source dataset
uspto-grants-2012_04
Patent number
US08163758B2

Reaction notes

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