Formaldehyde → Tert-butyl 3-methyl-3-(methyl(1-methyl-2-oxo-8-(trifluoromethyl)-3-((2-(tri methylsilyl)ethoxy)methyl)-1,2,3,5-tetrahydrobenzo[5,6][1,4]oxazino[3,4-c][1,2,4]triazin-9-yl)amino)azetidine-1-carboxylate

HRID 519060Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 519060
[C:1]([O:5][C:6]([N:8]1[CH2:11][C:10]([CH3:41])([NH:12][C:13]2[CH:14]=[C:15]3[C:24](=[CH:25][C:26]=2[C:27]([F:30])([F:29])[F:28])[O:23][CH2:22][C:21]2[N:16]3[CH:17]([CH3:40])[C:18](=[O:39])[N:19]([CH2:31][O:32][CH2:33][CH2:34][Si:35]([CH3:38])([CH3:37])[CH3:36])[N:20]=2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C=O.CO.[BH3-][C:47]#N.[Na+]>CC(O)C.CC(O)=O>[CH3:41][C:10]1([N:12]([CH3:47])[C:13]2[C:26]([C:27]([F:29])([F:28])[F:30])=[CH:25][C:24]3[O:23][CH2:22][C:21]4=[N:20][N:19]([CH2:31][O:32][CH2:33][CH2:34][Si:35]([CH3:36])([CH3:37])[CH3:38])[C:18](=[O:39])[CH:17]([CH3:40])[N:16]4[C:15]=3[CH:14]=2)[CH2:9][N:8]([C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:7])[CH2:11]1

Komponenten

7

Edukt 4

HCID 712FormaldehydeHCID 887MethanolHCID 5003444Sodium cyanoborohydrideHCID 867273933-Methyl-3-[4-methyl-3-oxo-7-trifluoromethyl-2-(2-trimethylsilanyl-ethoxymethyl)-2,3,4,10-tetrahydro-9-oxa-1,2,4a-triaza-phenanthren-6-ylamino]-azetidine-1-carboxylic acid tert-butyl ester

Produkt 1

HCID 86727426Tert-butyl 3-methyl-3-(methyl(1-methyl-2-oxo-8-(trifluoromethyl)-3-((2-(tri methylsilyl)ethoxy)methyl)-1,2,3,5-tetrahydrobenzo[5,6][1,4]oxazino[3,4-c][1,2,4]triazin-9-yl)amino)azetidine-1-carboxylateAusbeute 53 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 176Acetic AcidLösungsmittel2×HCID 3776IsopropanolLösungsmittel

Reaktionsbedingungen

Temperatur
110 °C

Versuchsvorschrift

A mixture of 3-methyl-3-[4-methyl-3-oxo-7-trifluoromethyl-2-(2-trimethylsilanyl-ethoxymethyl)-2,3,4,10-tetrahydro-9-oxa-1,2,4a-triaza-phenanthren-6-ylamino]-azetidine-1-carboxylic acid tert-butyl ester (Example #100, Step A, 0.250 g, 0.417 mmol) and paraformaldehyde (neat, 0.250 g, 8.34 mmol) in iPrOH (5 mL) and AcOH (0.5 ml) was stirred at 110° C. for 2 days. The reaction mixture was cooled to ambient temperature and the solvent was removed in vacuo. Then, MeOH (5 mL), AcOH (2.5 mL) and NaBH3CN (0.524 g, 8.34 mmol) were added. The mixture was stirred at 60° C. for 1 h. The reaction mixture was cooled to ambient temperature and solvent was removed in vacuo. The residue was purified by column chromatography on silica gel (eluting with 5-10% EtOAc in petroleum ether) to give tert-butyl 3-methyl-3-(methyl(1-methyl-2-oxo-8-(trifluoromethyl)-3-((2-(trimethylsilyl)ethoxy)methyl)-1,2,3,5-tetrahydrobenzo[5,6][1,4]oxazino[3,4-c][1,2,4]triazin-9-yl)amino)azetidine-1-carboxylate (0.135 g, 53%). 1H NMR (CDCl3, 400 MHz): δ 7.25 (s, 1H), 6.72 (s, 1H), 5.10 (m, 2H), 4.65 (m, 1H), 4.66 (q, J=13.2 Hz, 2H), 4.03 (d, J=8.8 Hz, 1H), 3.90 (d, J=12.4 Hz, 1H), 3.66 (t, 2H), 3.58 (t, 2H), 2.68 (s, 3H), 1.48 (s, 3H), 1.47 (d, J=6.4 Hz, 3H), 1.42 (s, 9H), 0.99 (m, 2H), 0.00 (s, 9H).

Aufarbeitung

  1. temperatureThe reaction mixture was cooled to ambient temperature
  2. customthe solvent was removed in vacuo
  3. stirringThe mixture was stirred at 60° C. for 1 h
  4. temperatureThe reaction mixture was cooled to ambient temperature
  5. customsolvent was removed in vacuo
  6. customThe residue was purified by column chromatography on silica gel (eluting with 5-10% EtOAc in petroleum ether)

Quellen und Nachweise

ORD-Eintrag
ord-bc209c7cac2042f9ba8e334817b9066a
Quelldatensatz
uspto-grants-2015_08
Patentnummer
US09115151B2

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