Dimethylformamide → 1'-Benzylspiro[benzo[b]pyrrolo[1,2-d][1,4]oxazine-4,4'-piperidine]-1-carbaldehyde

HRID 2204068Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2204068
O=P(Cl)(Cl)Cl.[CH2:6]([N:13]1[CH2:30][CH2:29][C:16]2([C:21]3=[CH:22][CH:23]=[CH:24][N:20]3[C:19]3[CH:25]=[CH:26][CH:27]=[CH:28][C:18]=3[O:17]2)[CH2:15][CH2:14]1)[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1.CN([CH:34]=[O:35])C>>[CH2:6]([N:13]1[CH2:30][CH2:29][C:16]2([O:17][C:18]3[CH:28]=[CH:27][CH:26]=[CH:25][C:19]=3[N:20]3[C:24]([CH:34]=[O:35])=[CH:23][CH:22]=[C:21]23)[CH2:15][CH2:14]1)[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1

Komponenten

4

Edukt 3

HCID 6228Dimethylformamide2×HCID 24813Phosphorus oxychlorideHCID 585510631-Benzylspiro[piperidine-4,4'-pyrrolo[2,1-c][1,4]benzoxazine]

Produkt 1

HCID 585509691'-Benzylspiro[benzo[b]pyrrolo[1,2-d][1,4]oxazine-4,4'-piperidine]-1-carbaldehydeAusbeute 86 %

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

N,N-Dimethylformamide (723 μL, 9.40 mmol), under nitrogen, was cooled to 0° C. and POCl3 (876 μL, 9.40 mmol) was added dropwise. The reaction was stirred for 20 min at 0° C. and a white solid formed. A solution of 1-benzylspiro[piperidine-4,4′-pyrrolo[2,1-c][1,4]benzoxazine] (2.07 g, 6.27 mmol) in dry DMF (15.5 mL) was added dropwise and the cooling bath was removed. The reaction mixture was stirred for 2 h at 50° C., then cooled down to room temperature and poured onto ice. Sodium hydroxide (1 M) was added until the pH reached 10, then the solution was acidified to pH 6 with 3 M HCl. The mixture was then extracted with EtOAc. The organics were dried over sodium sulfate, filtered and concentrated. The residue was purified by column chromatography (silica gel: 10-70% EtOAc in hexanes) to give 1′-benzylspiro[benzo[b]pyrrolo[1,2-d][1,4]oxazine-4,4′-piperidine]-1-carbaldehyde (1.94 g, 86%). ESI-MS m/z calc. 358.4, found 359.3 (M+1)+; Retention time: 1.16 minutes (3 min run). 1H NMR (400 MHz, CDCl3) δ 9.66 (s, 1H), 8.17-8.07 (m, 1H), 7.38-7.30 (m, 4H), 7.29-7.24 (m, 1H), 7.20-7.13 (m, 2H), 7.09 (m, 2H), 6.20 (d, J=4.1 Hz, 1H), 3.59 (s, 2H), 2.76 (m, 2H), 2.58-2.45 (m, 2H), 2.10-1.96 (m, 4H).

Aufarbeitung

  1. customa white solid formed
  2. customthe cooling bath was removed
  3. stirringThe reaction mixture was stirred for 2 h at 50° C.
  4. temperaturecooled down to room temperature
  5. additionpoured onto ice
  6. additionSodium hydroxide (1 M) was added until the pH
  7. extractionThe mixture was then extracted with EtOAc
  8. dry with materialThe organics were dried over sodium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customThe residue was purified by column chromatography (silica gel: 10-70% EtOAc in hexanes)

Quellen und Nachweise

ORD-Eintrag
ord-33dc1417f04f4d588b1445741293b0b7
Quelldatensatz
uspto-grants-2016_06
Patentnummer
US09365588B2

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