تفاعل #160200

معادلة التفاعل

tert-butyl 8-benzyl-10-vinyl-11-oxa-3,8-diazaspiro[5.5]undecane-3-carboxylate

HCl

4-isopropoxy-3-methyl-benzoic acid

dimethyl-ammonium hexafluorophosphate

Triethylamine

→

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

المردود 99.0%

المذيبات

ethanol

DMF

ظروف التفاعل

المعالجة

1. 1
   تركيزThe reaction mixture was concentrated in vacuo
2. 2
   workup.STIRRINGthe reaction mixture was stirred for 10 minutes
3. 3
   workup.STIRRINGthe reaction mixture was stirred overnight at room temperature
4. 4
   تركيزThe reaction mixture was concentrated in vacuo
5. 5
   workup.ADDITIONdiluted with DCM (5 mL)
6. 6
   غسيلwashed with 1 N aq. NaOH (2 mL) and brine (2 mL)
7. 7
   تجفيفdried over MgSO4
8. 8
   تركيزconcentrated in vacuo
9. 9
   أخرىThe residue was purified by silica gel column chromatography

الإجراء التجريبي

To tert-butyl 8-benzyl-10-vinyl-11-oxa-3,8-diazaspiro[5.5]undecane-3-carboxylate (600 mg, 1.61 mmol) in ethanol (1 mL) was added HCl (4 mL of 4 M in dioxane, 16.11 mmol) and the mixture was stirred for 30 minutes. The reaction mixture was concentrated in vacuo, then DMF (4 mL), 4-isopropoxy-3-methyl-benzoic acid (313 mg, 1.61 mmol) and dimethylamino(triazolo[4,5-b]pyridin-3-yloxy)methylene]-dimethyl-ammonium hexafluorophosphate (613 mg, 1.61 mmol) were added and the reaction mixture was stirred for 10 minutes. Triethylamine (898 μL, 6.44 mmol) was added and the reaction mixture was stirred overnight at room temperature. The reaction mixture was concentrated in vacuo, diluted with DCM (5 mL), washed with 1 N aq. NaOH (2 mL) and brine (2 mL), dried over MgSO4 and concentrated in vacuo. The residue was purified by silica gel column chromatography using 0-100% EtOAc/hexane as eluent to give (8-benzyl-10-vinyl-11-oxa-3,8-diazaspiro[5.5]undecan-3-yl)-(4-isopropoxy-3-methyl-phenyl)methanone as a pale yellow oil (715 mg, 99%). 1H NMR (400 MHz, CDCl3) δ 7.35-7.22 (m, 5H), 7.20-7.14 (m, 2H), 6.79 (d, J=8.2 Hz, 1H), 5.83-5.74 (m, 1H), 5.34-5.26 (m, 1H), 5.15 (d, J=10.6 Hz, 1H), 4.59-4.50 (m, 1H), 4.33-4.14 (m, 2H), 3.59-3.14 (m, 7H), 2.79 (d, J=11.0 Hz, 1H), 2.56 (d, J=11.1 Hz, 1H), 2.19 (s, 3H), 1.91-1.80 (m, 2H), 1.69-1.39 (m, 2H), 1.34 (d, J=6.0 Hz, 6H); ESI-MS m/z calc. 448.6. Found 449.5 (M+1)+; Retention time: 1.54 minutes (3 min run).

المصدر