Diisopropylethylamine → (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

HRID 2355486Notes

Reaction equation

HRID 2355486 reaction equation
[CH2:1]([C:3]1[CH:29]=[CH:28][CH:27]=[CH:26][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][NH:22][CH2:21]1)([OH:19])[CH2:13][CH2:14][CH2:15][CH2:16][O:17][CH3:18])[CH3:2].[N+](C1C=CC([O:37][C:38]([NH:40][C@H:41]([CH2:48][N:49]([CH3:59])[C:50]([O:52][CH2:53][CH2:54][Si:55]([CH3:58])([CH3:57])[CH3:56])=[O:51])[CH2:42][O:43][Si](C)(C)C)=O)=CC=1)([O-])=O.CCN(C(C)C)C(C)C>C(Cl)Cl>[CH2:1]([C:3]1[CH:29]=[CH:28][CH:27]=[CH:26][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:38]([NH:40][C@H:41]([CH2:48][N:49]([CH3:59])[C:50]([O:52][CH2:53][CH2:54][Si:55]([CH3:58])([CH3:57])[CH3:56])=[O:51])[CH2:42][OH:43])=[O:37])[CH2:21]1)([OH:19])[CH2:13][CH2:14][CH2:15][CH2:16][O:17][CH3:18])[CH3:2]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 59383027(S)-1-(2-(2-ethylphenoxy)phenyl)-5-methoxy-1-((R)-piperidin-3-yl)pentan-1-olHCID 67190521(2R)-2-(p-nitrophenoxycarbonylamino)-3-(N-methyl-N-(2-(trimethylsilyl)ethoxycarbonyl)amino)-1-(trimethylsilyloxy)propane

Product 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-carboxamideYield 30%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of (S)-1-(2-(2-ethylphenoxy)phenyl)-5-methoxy-1-((R)-piperidin-3-yl)pentan-1-ol (19.9 mg, 0.05 mmol) in CH2Cl2 (0.5 mL) was added the solution of (2R)-2-(p-nitrophenoxycarbonylamino)-3-(N-methyl-N-(2-(trimethylsilyl)ethoxycarbonyl)amino)-1-(trimethylsilyloxy)propane (0.05 mmol), followed by DIEA (26 μL, 0.15 mmol). The resulting yellow solution was stirred at rt for 30 min. CH2Cl2 was removed in vacuo and the residue was redissolved in acetonitrile, and purified by prep HPLC to give (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, 30%). MS m/z 672 (M+H+).

Workup

  1. customCH2Cl2 was removed in vacuo
  2. dissolutionthe residue was redissolved in acetonitrile
  3. custompurified by prep HPLC

Sources & evidence

ORD record
ord-86cbdbd52dd64773acda4c9e4459683f
Source dataset
uspto-grants-2010_07
Patent number
US07754737B2

Reaction notes

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