Ethanaminium, N,N,N-triethyl-, fluoride (1:1) → (3R)-3-((S)-1-(2-(2-ethylphenoxy)phenyl)-1-hydroxy-5-methoxypentyl)-N-((R)-1-hydroxy-3-(methylamino) propan-2-yl)piperidine-1-carboxamide

HRID 2355487Notes

Reaction equation

HRID 2355487 reaction equation
[CH2:1]([C:3]1[CH:47]=[CH:46][CH:45]=[CH:44][C:4]=1[O:5][C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][C:7]=1[C@:12]([C@@H:20]1[CH2:25][CH2:24][CH2:23][N:22]([C:26]([NH:28][C@H:29]([CH2:32][N:33](C)[C:34](OCC[Si](C)(C)C)=O)[CH2:30][OH:31])=[O:27])[CH2:21]1)([OH:19])[CH2:13][CH2:14][CH2:15][CH2:16][O:17][CH3:18])[CH3:2].[F-].C([N+](CC)(CC)CC)C>C(#N)C>[CH2:1]([C:3]1[CH:47]=[CH:46][CH:45]=[CH:44][C:4]=1[O:5][C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][C:7]=1[C@:12]([C@@H:20]1[CH2:25][CH2:24][CH2:23][N:22]([C:26]([NH:28][C@H:29]([CH2:32][NH:33][CH3:34])[CH2:30][OH:31])=[O:27])[CH2:21]1)([OH:19])[CH2:13][CH2:14][CH2:15][CH2:16][O:17][CH3:18])[CH3:2]

Participants

4

Reactant 2

HCID 69582Ethanaminium, N,N,N-triethyl-, fluoride (1:1)HCID 67191764(3R)-3-((S)-1-(2-(2-ethylphenoxy)phenyl)-1-hydroxy-5-methoxypentyl)-N-((R)-1-hydroxy-3-(N-methyl-N-(2-(trimethylsilyl)ethoxycarbonyl)amino)propan-2-yl)piperidine-1-carboxamide

Product 1

HCID 57544899(3R)-3-((S)-1-(2-(2-ethylphenoxy)phenyl)-1-hydroxy-5-methoxypentyl)-N-((R)-1-hydroxy-3-(methylamino) propan-2-yl)piperidine-1-carboxamideYield 37.9%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
50 °C

Procedure

To a solution of (3R)-3-((S)-1-(2-(2-ethylphenoxy)phenyl)-1-hydroxy-5-methoxypentyl)-N—((R)-1-hydroxy-3-(N-methyl-N-(2-(trimethylsilyl)ethoxycarbonyl)amino)propan-2-yl)piperidine-1-carboxamide (10.0 mg, 0.01 mmol) in acetonitrile (1.0 mL) was added excess tetraethylammonium fluoride. The resulting solution was heated at 50° C. for 2 h, and concentrated under vacuum. The residue was purified by prep HPLC to give (3R)-3-((S)-1-(2-(2-ethylphenoxy)phenyl)-1-hydroxy-5-methoxypentyl)-N—((R)-1-hydroxy-3-(methylamino)propan-2-yl)piperidine-1-carboxamide (2 mg) as its TFA salt. 1H NMR (400 MHz, CD3OD) 7.62 (d, 1H), 7.32 (d, 1H), 7.04-7.20 (m, 4H), 6.74 (d, 1H), 6.56 (d, 1H), 4.40 (d, 1H), 4.00 (m, 1H), 3.92 (d, 1H), 3.60 (m, 1H), 3.54 (m, 1H), 3.26 (t, 2H), 3.24 (s, 3H), 3.22 (m, 1H), 3.04 (m, 1H), 2.82 (m, 1H), 2.64 (s, 3H), 2.62 (q, 2H), 2.42 (m, 2H), 1.94 (m, 1H), 1.24-1.64 (m, 7H), 1.08 (t, 3H), 0.98 (m, 1H); MS m/z 528 (M+H+).

Workup

  1. concentrationconcentrated under vacuum
  2. customThe residue was purified by prep HPLC

Sources & evidence

ORD record
ord-6f96515614094d20840385b69443d142
Source dataset
uspto-grants-2010_07
Patent number
US07754737B2

Reaction notes

Loading…