Reaktion #160220

Reaktionsgleichung

T3P

8-benzyl-3-(4-isopropoxy-3-methyl-benzoyl)-11-oxa-3,8-diazaspiro[5.5]undecane-10-carboxylic acid

N′-hydroxyacetamidine

triethylamine

→

[8-benzyl-10-(3-methyl-1,2,4-oxadiazol-5-yl)-11-oxa-3,8-diazaspiro[5.5]undecan-3-yl]-(4-isopropoxy-3-methyl-phenyl)methanone

Ausbeute 39.1%

Lösungsmittel

2-methyltetrahydrofuran

Reaktionsbedingungen

Aufarbeitung

1. 1
   TemperaturThe reaction mixture was cooled to room temperature
2. 2
   Sonstigepartitioned between EtOAc/saturated aq. NaHCO3
3. 3
   SonstigeThe layers were separated
4. 4
   Extraktionthe aqueous layer was extracted with EtOAc (2×)
5. 5
   TrocknenThe combined organics were dried over Na2SO4
6. 6
   Filtrationfiltered
7. 7
   Einengenconcentrated in vacuo to a dark foam
8. 8
   SonstigeThe crude product was purified by silica gel column chromatography

Vorschrift

T3P (546 mg, 510 μL of 50% w/w, 0.86 mmol) was added to a solution of 8-benzyl-3-(4-isopropoxy-3-methyl-benzoyl)-11-oxa-3,8-diazaspiro[5.5]undecane-10-carboxylic acid (160 mg, 0.34 mmol), N′-hydroxyacetamidine (25 mg, 0.34 mmol) and triethylamine (173 mg, 239 μL, 1.71 mmol) in 2-methyltetrahydrofuran (800 μL) and the reaction mixture was heated at 75° C. for 2 hours. The reaction mixture was cooled to room temperature and partitioned between EtOAc/saturated aq. NaHCO3. The layers were separated and the aqueous layer was extracted with EtOAc (2×). The combined organics were dried over Na2SO4, filtered and concentrated in vacuo to a dark foam. The crude product was purified by silica gel column chromatography using 0-30% EtOAc in DCM as eluent to afford [8-benzyl-10-(3-methyl-1,2,4-oxadiazol-5-yl)-11-oxa-3,8-diazaspiro[5.5]undecan-3-yl]-(4-isopropoxy-3-methyl-phenyl)methanone (67 mg, 39%) as a white solid. ESI-MS m/z calc. 504.6. Found 505.3 (M+1)+; Retention time: 1.63 minutes (3 min run).

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