Formaldehyde → HCID 86750811, compound

HRID 1780353Notes

Reaction equation

HRID 1780353 reaction equation
[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]

Participants

5

Reactant 3

HCID 712FormaldehydeHCID 516892Sodium BicarbonateHCID 22872639HCID 22872639, compound

Product 1

HCID 86750811HCID 86750811, compoundYield 64%

Reagents, catalysts & solvents 1

HCID 284Formic AcidSolvent

Conditions

Temperature
70 °C

Procedure

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).

Workup

  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

Sources & evidence

ORD record
ord-b11c860333284c80973b198acded2683
Source dataset
uspto-grants-1997_05
Patent number
US05629325

Reaction notes

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