Formic Acid → 3-((2(RS)-(Phenoxymethyl)morpholin-4-yl)methyl)-quinoline Hydrogen Oxalate

HRID 977082

反応式

HRID 977082 の反応式
[N:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[C:3]([CH:11]=[O:12])[CH:2]=1.[O:13]([CH2:20][CH:21]1[O:26][CH2:25][CH2:24][NH:23][CH2:22]1)[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1.Cl.[CH:28]([OH:30])=[O:29]>>[C:11]([OH:12])(=[O:13])[C:28]([OH:30])=[O:29].[O:13]([CH2:20][CH:21]1[O:26][CH2:25][CH2:24][N:23]([CH2:11][C:3]2[CH:2]=[N:1][C:10]3[C:5]([CH:4]=2)=[CH:6][CH:7]=[CH:8][CH:9]=3)[CH2:22]1)[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1

参加物

5

反応物 4

HCID 284Formic AcidHCID 313Hydrochloric AcidHCID 836413-QuinolinecarboxaldehydeHCID 220117952-(Phenoxymethyl)morpholine

生成物 1

HCID 199644143-((2(RS)-(Phenoxymethyl)morpholin-4-yl)methyl)-quinoline Hydrogen Oxalate

実験手順

Quinoline-3-carboxaldehyde (447 mg, 2.8 mmol), 2(RS)-(phenoxymethyl)morpholine (500 mg, 2.59 mmol) and anhydrous formic acid (0.1 ml) were heated at 120° C. (oil bath temperature), with stirring, for 6 hours. The reaction mixture was cooled, 2M hydrochloric acid (20 ml) added and the solution washed with ethyl acetate (20 ml). The aqueous was basified to pH=11 with 2M aqueous sodium hydroxide, then extracted with ethyl acetate (2×30 ml). The combined organics were dried (sodium sulphate) then evaporated to give a gum which was purified by column chromatography on silica (200 g) using ethyl acetate to ethyl acetate/methanol (25:1) to afford the title compound free base as a pale yellow gum (340 mg, 36%). The hydrogen oxalate salt had mp 164°-166° C. (ethanol/water). MS CI+, m/z=335 for (M+H)+. 1H NMR (360 MHz, DMSO-d6) δ2.23 (1H, dd, J1 =J2 ==11 Hz), 2.35 (1H, ddd, J1 =3, J2 =J3 =11 Hz), 2.80 (1H, d, J=11 Hz), 2.97 (1H, d, J=11 Hz), 3.61 (1H, ddd, J1 =2, J2 =J3 =11 Hz), 3.80-3.92 (4H, m), 3.96 (2H, d, J=5 Hz), 6.89-6.94 (3H, m), 7.23-7.28 (2H, m), 7.59-7.64 (1H, m), 7.73-7.78 (1H, m), 7.97-8.04 (2H, m), 8.29 (1H, d, J=2 Hz), 8.90 (1H, d, J=2 Hz). Found: C, 63.38; H, 5.84; N, 6.48. C21H22N2O2.C2H2O4.0.5H2O requires C, 63.73; H, 5.81; N, 6.46%.

後処理

  1. temperatureThe reaction mixture was cooled
  2. washthe solution washed with ethyl acetate (20 ml)
  3. extractionextracted with ethyl acetate (2×30 ml)
  4. dry with materialThe combined organics were dried (sodium sulphate)
  5. customthen evaporated
  6. customto give a gum which
  7. customwas purified by column chromatography on silica (200 g)

出典と根拠

ORDレコード
ord-78bcd37269d241c289a57cdc2c30f5b6
出典データセット
uspto-grants-1997_03
特許番号
US05614518

関連ノート

読み込み中…