Trimethyl borate → Cyclopropyl-(4-hydroxymethyl-piperidin-1-yl)-methanone

HRID 487564

Reaktionsgleichung

Reaktionsgleichung von HRID 487564
[CH:1]1([C:4]([N:6]2[CH2:11][CH2:10][CH:9]([C:12](OCC)=[O:13])[CH2:8][CH2:7]2)=[O:5])[CH2:3][CH2:2]1.[BH4-].[Li+].B(OC)(OC)OC>O1CCCC1.O>[CH:1]1([C:4]([N:6]2[CH2:7][CH2:8][CH:9]([CH2:12][OH:13])[CH2:10][CH2:11]2)=[O:5])[CH2:2][CH2:3]1

Komponenten

6

Edukt 3

HCID 8470Trimethyl borateHCID 4148881Lithium borohydrideHCID 10036613Ethyl 1-(cyclopropylcarbonyl)piperidine-4-carboxylate

Produkt 1

HCID 10012597Cyclopropyl-(4-hydroxymethyl-piperidin-1-yl)-methanoneAusbeute 63,7 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 962WaterLösungsmittel2×HCID 8028TetrahydrofuranLösungsmittel2×

Versuchsvorschrift

A solution of 1-(cyclopropylcarbonyl)-4-carboethoxy piperidine (35 g, 156 mmol) in anhydrous tetrahydrofuran (350 mi) was stirred at ambient temperature under a nitrogen atmosphere. A solution of lithium borohydride in tetrahydrofuran (2 M, 78 ML, 156 mmol) was added dropwise. Trimethyl borate (1.77 mL, 15.7 mmol) was added, then the reduction mixture was stirred for about 48 hours. Water was added dropwise with vigorous stirring until the vigorous gas evolution ceased. The mixture was diluted twofold with water and extracted three times with ethyl acetate. The combined organic layers were dried over magnesium sulfate, filtered and concentrated in vacuo. Vacuum distillation (bp 165° C., 0.5 mm Hg) gave a clear, colorless liquid (18.2 g):IR (neat): 3410 (br s), 3094 (w), 3008 (s), 2918 (s), 2858 (s), 1738 (m), 1613 (s), 1448 (s), 1375 (s), 1316 (s); 1H-NMR: 4.7-4.5 (m, 1H), 4.4-4.1 (m, 1H), 3.6-3.4 (m, 2H), 3.2-2.5 (m, 3H), 2.0-1.7 (m, 4H), 1.4-1.1 (m, 1H), 1.0-0.8 (m, 2H), 0.8-0.65 (m, 2H); HRMS:Calcd for C10H17NO2 :183.1259; Found: 183.1250; Anal.:Calcd for C10H17NO2 : C, 65.54, H, 9.35, N, 7.64; Found: C, 65.83, H, 9.43, N, 7.50.

Aufarbeitung

  1. stirringwith vigorous stirring until the vigorous gas evolution
  2. extractionextracted three times with ethyl acetate
  3. dry with materialThe combined organic layers were dried over magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. distillationVacuum distillation (bp 165° C., 0.5 mm Hg)

Quellen und Nachweise

ORD-Eintrag
ord-24012add6bc84c88bc85f585beb9a09a
Quelldatensatz
uspto-grants-1994_03
Patentnummer
US05296479

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