Reaktion #160238

Reaktionsgleichung

NaBH(OAc)3

(4-isopropoxy-3-methyl-phenyl)-[10-(methoxymethyl)-11-oxa-3,8-diazaspiro[5.5]undecan-3-yl]methanone

cyclobutanone

acetic acid

→

(4-cyclobutyl-2-(methoxymethyl)-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)(4-isopropoxy-3-methylphenyl)methanone

Ausbeute 84.0%

Lösungsmittel

dichloroethane

MTBE

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.STIRRINGthe reaction mixture stirred for 16 h
2. 2
   Waschenwashed with 1N NaOH (100 mL)
3. 3
   SonstigeThe organic layer was separated
4. 4
   Waschenwashed with brine
5. 5
   Trocknendried over Na2SO4
6. 6
   Filtrationfiltered
7. 7
   Einengenconcentrated in vacuo

Vorschrift

A solution of (4-isopropoxy-3-methyl-phenyl)-[10-(methoxymethyl)-11-oxa-3,8-diazaspiro[5.5]undecan-3-yl]methanone (343 mg, 0.912 mmol) and cyclobutanone (96.0 mg, 1.36 mmol) in dichloroethane (3 mL) was treated with acetic acid (78 μL, 1.4 mmol) and stirred for 30 min. NaBH(OAc)3 (387 mg, 1.82 mmol) was added and the reaction mixture stirred for 16 h. The reaction mixture was diluted with MTBE and washed with 1N NaOH (100 mL). The organic layer was separated and washed with brine, dried over Na2SO4, filtered and concentrated in vacuo. Silica gel chromatography (5-80% ethyl acetate/hexane) provided (4-cyclobutyl-2-(methoxymethyl)-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)(4-isopropoxy-3-methylphenyl)methanone (330 mg, 84%). ESI-MS m/z calc. 430.3. Found 431.3 (M+1)+; Retention time: 1.24 minutes (3 min run). 1H NMR (400 MHz, CDCl3) δ 7.19 (d, J=8.4 Hz, 2H), 6.80 (d, J=8.1 Hz, 1H), 4.55 (hept, J=6.2 Hz, 1H), 4.30-4.10 (m, 1H), 3.94-3.75 (m, 1H), 3.62-3.46 (m, 1H), 3.48-3.33 (m, 6H), 3.30-3.16 (m, 1H), 2.75 (d, J=10.8 Hz, 1H), 2.67-2.57 (m, 1H), 2.55 (d, J=11.1 Hz, 1H), 2.47-2.27 (m, 1H), 2.20 (s, 3H), 1.98 (d, J=7.3 Hz, 2H), 1.91-1.76 (m, 1H), 1.76-1.61 (m, 4H), 1.57-1.39 (m, 3H), 1.34 (d, J=6.0 Hz, 6H).

Quelle