Chlorotrimethylsilane → (3R)-3-((S)-1-(3-fluorophenyl)-1-hydroxy-5-methoxypentyl)-N-(3-(1-hydroxycyclohexyl)-1-(N-methyl-N-(2-(trimethylsilyl)ethoxycarbonyl)amino)propan-2-yl)piperidine-1-carboxamide

HRID 1254371Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1254371
[OH:1][C:2]1([CH2:8][CH:9]([NH2:22])[CH2:10][N:11]([CH3:21])[C:12](=[O:20])[O:13][CH2:14][CH2:15][Si:16]([CH3:19])([CH3:18])[CH3:17])[CH2:7][CH2:6][CH2:5][CH2:4][CH2:3]1.C[Si](Cl)(C)C.Cl[C:29](OC1C=CC([N+]([O-])=O)=CC=1)=[O:30].Cl.[F:42][C:43]1[CH:44]=[C:45]([C@:49]([C@@H:57]2[CH2:62][CH2:61][CH2:60][NH:59][CH2:58]2)([OH:56])[CH2:50][CH2:51][CH2:52][CH2:53][O:54][CH3:55])[CH:46]=[CH:47][CH:48]=1>C(Cl)Cl.CCN(CC)CC>[F:42][C:43]1[CH:44]=[C:45]([C@:49]([C@@H:57]2[CH2:62][CH2:61][CH2:60][N:59]([C:29]([NH:22][CH:9]([CH2:8][C:2]3([OH:1])[CH2:3][CH2:4][CH2:5][CH2:6][CH2:7]3)[CH2:10][N:11]([CH3:21])[C:12]([O:13][CH2:14][CH2:15][Si:16]([CH3:17])([CH3:19])[CH3:18])=[O:20])=[O:30])[CH2:58]2)([OH:56])[CH2:50][CH2:51][CH2:52][CH2:53][O:54][CH3:55])[CH:46]=[CH:47][CH:48]=1

Komponenten

7

Edukt 4

HCID 6397ChlorotrimethylsilaneHCID 821294-Nitrophenyl chloroformateHCID 67189342HCID 67189342, VerbindungHCID 67192771(S)-1-(3-fluorophenyl)-5-methoxy-1-((R)-piperidin-3-yl)pentan-1-ol hydrochloride

Produkt 1

HCID 67189295(3R)-3-((S)-1-(3-fluorophenyl)-1-hydroxy-5-methoxypentyl)-N-(3-(1-hydroxycyclohexyl)-1-(N-methyl-N-(2-(trimethylsilyl)ethoxycarbonyl)amino)propan-2-yl)piperidine-1-carboxamideAusbeute 50 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6344DichloromethaneLösungsmittelHCID 8471TriethylamineLösungsmittel

Versuchsvorschrift

To a solution of 2-(trimethylsilyl)ethyl 3-(1-hydroxycyclohexyl)-2-amino-propylmethylcarbamate (18.3 mg, 0.055 mmol) in CH2Cl2 (2 mL) was added Et3N (0.2 mL) and TMSCl (12 mg, 14 μL, 0.11 mmol). The resulting solution was stirred for 1 h and evaporated under vacuum. The residue was dissolved in CH2Cl2 (2 mL) and pyridine (0.05 mL) was added, followed by 4-nitrophenyl chloroformate (13.5 mg, 0.66 mmol). The solution was stirred for 30 min and (S)-1-(3-fluorophenyl)-5-methoxy-1-((R)-piperidin-3-yl)pentan-1-ol hydrochloride (18 mg, 0.055 mmol). The resulting mixture was stirred for 10 min and evaporated. The residue was purified by prep HPLC to give (3R)-3-((S)-1-(3-fluorophenyl)-1-hydroxy-5-methoxypentyl)-N-(3-(1-hydroxycyclohexyl)-1-(N-methyl-N-(2-(trimethylsilyl)ethoxycarbonyl)amino)propan-2-yl)piperidine-1-carboxamide (17.8 mg, 50%). MS m/z 652 (M+H+).

Aufarbeitung

  1. customevaporated under vacuum
  2. dissolutionThe residue was dissolved in CH2Cl2 (2 mL)
  3. additionpyridine (0.05 mL) was added
  4. stirringThe solution was stirred for 30 min
  5. stirringThe resulting mixture was stirred for 10 min
  6. customevaporated
  7. customThe residue was purified by prep HPLC

Quellen und Nachweise

ORD-Eintrag
ord-40e17cfef3ff4d509d6bf42baaade0b8
Quelldatensatz
uspto-grants-2013_06
Patentnummer
US08455521B2

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