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 1254368Notes

Reaction equation

HRID 1254368 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-aa565f9d82d4428096a7e78c7468635a
Source dataset
uspto-grants-2013_06
Patent number
US08455521B2

Reaction notes

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