Diisopropylethylamine → tert-butyl (S)-1-((R)-3-((S)-1-(3-chlorophenyl)-1-hydroxy-5-methoxypentyl)piperidine-1-carboxamido)-3-cyclohexylpropan-2-ylcarbamate

HRID 1254383Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1254383
[Cl:1][C:2]1[CH:3]=[C:4]([C@:8]([C@@H:16]2[CH2:21][CH2:20][CH2:19][NH:18][CH2:17]2)([OH:15])[CH2:9][CH2:10][CH2:11][CH2:12][O:13][CH3:14])[CH:5]=[CH:6][CH:7]=1.[N+](C1C=CC([O:29][C:30]([NH:32][CH2:33][C@@H:34]([NH:42][C:43](=[O:49])[O:44][C:45]([CH3:48])([CH3:47])[CH3:46])[CH2:35][CH:36]2[CH2:41][CH2:40][CH2:39][CH2:38][CH2:37]2)=O)=CC=1)([O-])=O.CCN(C(C)C)C(C)C>CC#N.C(Cl)Cl.CCOCC>[Cl:1][C:2]1[CH:3]=[C:4]([C@:8]([C@@H:16]2[CH2:21][CH2:20][CH2:19][N:18]([C:30]([NH:32][CH2:33][C@@H:34]([NH:42][C:43](=[O:49])[O:44][C:45]([CH3:47])([CH3:46])[CH3:48])[CH2:35][CH:36]3[CH2:37][CH2:38][CH2:39][CH2:40][CH2:41]3)=[O:29])[CH2:17]2)([OH:15])[CH2:9][CH2:10][CH2:11][CH2:12][O:13][CH3:14])[CH:5]=[CH:6][CH:7]=1

Komponenten

7

Edukt 3

HCID 81531DiisopropylethylamineHCID 59382814(S)-1-(3-chlorophenyl)-5-methoxy-1-((R)-piperidin-3-yl)pentan-1-olHCID 59382967(S)-4-nitrophenyl 2-(t-butoxycarbonylamino)-3-cyclohexylpropylcarbamate

Produkt 1

HCID 86626201tert-butyl (S)-1-((R)-3-((S)-1-(3-chlorophenyl)-1-hydroxy-5-methoxypentyl)piperidine-1-carboxamido)-3-cyclohexylpropan-2-ylcarbamateAusbeute 49 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 3283Diethyl EtherLösungsmittelHCID 6342AcetonitrileLösungsmittelHCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

To a stirred solution of (S)-1-(3-chlorophenyl)-5-methoxy-1-((R)-piperidin-3-yl)pentan-1-ol (31 mg, 0.10 mmol) and (S)-tert-butyl 1-(p-nitrophenoxycarbonylamino)-3-cyclohexylpropan-2-ylcarbamate (40 mg, 0.10 mmol) in MeCN (1 mL) and CH2Cl2 (1 mL) was added DIEA (50 μL, 0.28 mmol). The mixture was stirred at rt for 20 h, diluted with ether (90 mL), washed with 5% aq HCl (20 mL) and 1 M aq NaOH (20 mL) and dried over MgSO4. Removal of the solvent left an oil (82 mg) which was applied to a 2-g silica SPE cartridge which was eluted sequentially with 10, 25, 50, 75 and 100% ethyl acetate in hexanes (15 mL of each) to afford 5 fractions. The 4th fraction was concentrated to afford tert-butyl (S)-1-((R)-3-((S)-1-(3-chlorophenyl)-1-hydroxy-5-methoxypentyl)piperidine-1-carboxamido)-3-cyclohexylpropan-2-ylcarbamate (29 mg, 49%) as an oil.

Aufarbeitung

  1. washwashed with 5% aq HCl (20 mL) and 1 M aq NaOH (20 mL)
  2. dry with materialdried over MgSO4
  3. customRemoval of the solvent
  4. waitleft an oil (82 mg) which
  5. washwas eluted sequentially with 10, 25, 50, 75 and 100% ethyl acetate in hexanes (15 mL of each)
  6. customto afford 5 fractions
  7. concentrationThe 4th fraction was concentrated

Quellen und Nachweise

ORD-Eintrag
ord-6389c46412624995b112628bf42fdfee
Quelldatensatz
uspto-grants-2013_06
Patentnummer
US08455521B2

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