Formaldehyde → HCID 86750809, 화합물

HRID 1780346노트

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HRID 1780346 반응식
[Br:1][C:2]1[CH:3]=[C:4]([O:9][CH2:10][C@H:11]2[CH2:15][CH2:14][CH2:13][N:12]2[C:16](OC(C)(C)C)=O)[CH:5]=[N:6][C:7]=1[Cl:8].C=O>C(O)=O>[ClH:8].[Br:1][C:2]1[CH:3]=[C:4]([O:9][CH2:10][C@H:11]2[CH2:15][CH2:14][CH2:13][N:12]2[CH3:16])[CH:5]=[N:6][C:7]=1[Cl:8]

참가 물질

4

반응물 2

HCID 712FormaldehydeHCID 22872666HCID 22872666, 화합물

생성물 1

HCID 86750809HCID 86750809, 화합물수율 119.1%

시약·촉매·용매 1

HCID 284Formic Acid용매

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온도
70 °C

실험 절차

To 5-bromo-6-chloro-3-(1-BOC-2-(R)-pyrrolidinylmethoxy)pyridine from step 69a (210 mg, 0.54 mmol) was added formalin (37%, 7 mL) and formic acid (3.5 mL), and the mixture was heated at 70° C. for 2.5 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 100:5-100:10 to afford to give the free base of the title compound (110 mg, 67% yield). MS (DCI/NH3) m/z 305/307 (M+H)+. 1H NMR (CDCl3, 300 MHz) δ1.68 (m, 3H), 2.02 (m, 1H), 2.32 (m, 1H), 2.48 (s, 3H), 2.67 (m, 1H), 3.12 (m, 1H), 3.96 (m, 2H), 7.52 (m, 1H), 8.06 (m, 1H). The base was converted to the salt by treatment with hydrogen chloride in THF to give the title compound. MS (DCI/NH3) m/z 305/207 (M+H)+. 1 H NMR (D2O, 300 MHz) δ: 2.20-2.17 (m, 2H), 2.18-2.31 (m, 1H), 2.32-2.47 (m, 1H), 3.03 (s, 3H), 3.27 (m, 1H), 3.73 (m, 1H), 3.96 (m, 1H), 4.36 (dd, J=6.1, 11.2 Hz, 1H), 4.53 (dd, J=3.1, 11.2 Hz, 1H), 7.91 (d, J=2.7 Hz, 1H), 8.13 (d, J=2.7 Hz, 1H). Anal. Calcd for C11H14N2OBrCl·1.1 HCl: C, 38.22; H, 4.40; N, 8.10. Found: C, 37.95; H, 4.81; N, 7.76. [α]25D =+11.06° (c 0.24, MeOH).

후처리

  1. concentrationThe solvent was concentrated
  2. additionsolid NaHCO3 was added to the residue
  3. extractionAt pH 8 the mixture was extracted with methylene chloride, which
  4. dry with materialwas dried over MgSO4
  5. concentrationconcentrated
  6. customThe residue was chromatographed on a silica gel column
  7. washeluting with methylene chloride:methanol 100:5-100:10
  8. customto afford

출처 및 근거

ORD 기록
ord-287b3ad901fa4f538da61dec59d3a069
출처 데이터셋
uspto-grants-1997_05
특허 번호
US05629325

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