Formaldehyde → HCID 86750811、化合物

HRID 1780353ノート

反応式

HRID 1780353 の反応式
[C:1]([C:9]1[CH:10]=[C:11]([O:16][CH2:17][C@H:18]2[CH2:22][CH2:21][CH2:20][N:19]2[C:23](OC(C)(C)C)=O)[CH:12]=[N:13][C:14]=1[Cl:15])#[C:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH3:8].C=O.C([O-])(O)=O.[Na+]>C(O)=O>[ClH:15].[ClH:15].[C:1]([C:9]1[CH:10]=[C:11]([O:16][CH2:17][C@H:18]2[CH2:22][CH2:21][CH2:20][N:19]2[CH3:23])[CH:12]=[N:13][C:14]=1[Cl:15])#[C:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH3:8]

参加物

5

反応物 3

HCID 712FormaldehydeHCID 516892Sodium BicarbonateHCID 22872639HCID 22872639、化合物

生成物 1

HCID 86750811HCID 86750811、化合物収率 64%

試薬・触媒・溶媒 1

HCID 284Formic Acid溶媒

反応条件

温度
70 °C

実験手順

To 5-(1-octynyl)-6-chloro-3-(1-BOC-2-(R)-pyrrolidinylmethoxy)pyridine from Example 79a (330 mg, 0.78 mmol) was added formalin (37%, 9 mL) and formic acid (4.5 mL), and the mixture was heated at 70° C. for 2 hours. The solvent was concentrated,and solid NaHCO3 was added to the residue. At pH 8 the mixture was extracted with methylene chloride, which was dried over MgSO4 and concentrated. The residue was chromatographed on a silica gel column, eluting with methylene chloride:methanol 100:1-100:3 to afford to give the free base of the title compound (166.5 mg (64% yield). MS (DCI/NH3) m/z 321 (M+)+. 1H NMR (CDCl3, 300 MHz) δ0.92 (m, 3H), 1.32 (m, 4H), 1.48 (m, 2H), 1.62 (m, 2H), 1.80 (m, 4H), 2.02 (m, 1H), 2.30 (m, 1H), 2.45 (m, 1H), 2.47 (s, 3H), 2.66 (m, 1H), 3.12 (m, 1H), 3.93 (m, 2H), 7.27 (m, 1H), 7.98 (m, 1H). The base was converted to the salt by treatment with HCl in ether to give the title compound. mp 114°-116° C. (dec). MS (DCI/NH3) m/z 335 (M+H)+. 1 H NMR (D2O, 300 MHz) δ: 1.02 (t, J=6.7 Hz, 3H), 1.43 (m, 4H), 1.58 (m, 2H), 1.71 (m, 2H), 2.06 (m, 1H), 2.21 (m, 2H), 2.42 (m, 1H, 2.56 (t, J=6.7 Hz, 2H), 3.06 (s, 3H), 3.28 (m, 1H), 3.77 (m, 1H), 3.87 (m, 1H), 4.41 (m, 2H), 7.50 (m, 1H), 8.12 (d, J=2.4 Hz, 1H). Anal. Calcd for C19H27N2OCl·1.5 HCl: C, 58.58; H, 7.37; N, 7.19. Found: C, 58.64; H, 7.39; N, 7.20. [α]25D =+8.99° (c 0.64, MeOH).

後処理

  1. additionwas added to the residue
  2. extractionAt pH 8 the mixture was extracted with methylene chloride, which
  3. dry with materialwas dried over MgSO4
  4. concentrationconcentrated
  5. customThe residue was chromatographed on a silica gel column
  6. washeluting with methylene chloride:methanol 100:1-100:3
  7. customto afford

出典と根拠

ORDレコード
ord-b11c860333284c80973b198acded2683
出典データセット
uspto-grants-1997_05
特許番号
US05629325

反応ノート

読み込み中…