Formaldehyde → HCID 86750811, 화합물

HRID 1780353노트

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HRID 1780353 반응식
[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]

참가 물질

5

반응물 3

HCID 712FormaldehydeHCID 516892Sodium BicarbonateHCID 22872639HCID 22872639, 화합물

생성물 1

HCID 86750811HCID 86750811, 화합물수율 64%

시약·촉매·용매 1

HCID 284Formic Acid용매

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온도
70 °C

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-b11c860333284c80973b198acded2683
출처 데이터셋
uspto-grants-1997_05
특허 번호
US05629325

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