Formaldehyde → HCID 86750810, compound

HRID 2305133Notes

Reaction equation

HRID 2305133 reaction equation
[CH3:1][C:2]([CH3:29])([CH3:28])[CH:3]=[CH:4][CH:5]=[CH:6][C:7]1[CH:8]=[C:9]([O:14][CH2:15][C@H:16]2[CH2:20][CH2:19][CH2:18][N:17]2[C:21](OC(C)(C)C)=O)[CH:10]=[N:11][C:12]=1[Cl:13].C=O>C(O)=O>[ClH:13].[ClH:13].[CH3:1][C:2]([CH3:29])([CH3:28])[CH:3]=[CH:4][CH:5]=[CH:6][C:7]1[CH:8]=[C:9]([O:14][CH2:15][C@H:16]2[CH2:20][CH2:19][CH2:18][N:17]2[CH3:21])[CH:10]=[N:11][C:12]=1[Cl:13]

Participants

4

Reactant 2

HCID 712FormaldehydeHCID 54433303HCID 54433303, compound

Product 1

HCID 86750810HCID 86750810, compoundYield 156.9%

Reagents, catalysts & solvents 1

HCID 284Formic AcidSolvent

Conditions

Temperature
70 °C

Procedure

To 5-(5,5-dimethyl-1,3-hexadienyl)-6-chloro-3-(1-BOC-2-(R)-pyrrolidinylmethoxy)pyridine from step 77a (145 mg, 0.34 mmol) was added formalin (37%, 4 mL) and formic acid (2 mL), and the mixture was heated at 70° C. for 3 hours. The solvent was concentrated, and solid NaHCO3 was added to the residue. At pH 8 the mixture was extracted with CH2Cl2, which was dried over MgSO4 and concentrated. The residue was chromatographed on a silica gel column, eluting with CH2Cl2:MeOH 100:4 to afford to give the free base of the title compound (72.5 mg, 66% yield). MS (CI/NH3) m/z 335 (M+H)+. 1H NMR (CDCl3, 300 MHz) δ 1.10 (s, 9H), 1.77 (m, 2H), 2.00 (m, 1H), 2.28 (m, 1H), 2.45 (m, 3H), 2.70 (m, 1H), 3.10 (m, 1H), 3.43 (m, 1H), 4.00 (m, 1H), 4.38 (m, 1H), 5.95 (m, 1H), 6.20 (m, 1H), 6.70 (m, 2H), 7.38 (m, 1H), 7.93 (m, 1H). The base was converted to the salt by treatment with hydrogen chloride in Et2O/THF to give the title compound. mp 194° C. (dec). MS (CI/NH3) m/z 335 (M+H)+. 1H NMR (D2O, 300 MHz) δ: 1.07 (s, 9H), 1.78-2.05 (m, 2H) 2.17-2.28 (m, 1H), 2.90 (dd, J=5.1, 31.9 Hz, 3H), 3.12 (m, 1H), 3.50 (m, 3H), 4.41 (m, 2H), 6.04 (d, J=15.6 Hz, 1H), 6.30 (dd, J=10.2, 15.2 Hz, 1H), 6.70 (d, J-15.6 Hz, 1H), 7.10 (ss, J=10.2, 15.6 Hz, 1H), 7,.84 (d, J=3.0 Hz, 1H), 8.06 (d, J=3.1 Hz, 1H). Anal. Calcd for C19H27N2OCl.1.7 HCl.0.8 Et2O: C, 58.45; H, 8.11; N, 6.14. Found: C, 58.58; H, 8.11; N, 5.85. [α]25D=+6.95° (c 0.71, MeOH).

Workup

  1. concentrationThe solvent was concentrated
  2. additionsolid NaHCO3 was added to the residue
  3. extractionAt pH 8 the mixture was extracted with CH2Cl2, which
  4. dry with materialwas dried over MgSO4
  5. concentrationconcentrated
  6. customThe residue was chromatographed on a silica gel column
  7. washeluting with CH2Cl2:MeOH 100:4
  8. customto afford

Sources & evidence

ORD record
ord-64252b20e5124b09abd784b31762cbd9
Source dataset
uspto-grants-2002_08
Patent number
US06437138B1

Reaction notes

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