Formaldehyde → HCID 86750810, compound

HRID 1780351Notes

Reaction equation

HRID 1780351 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 methylene chloride, which was dried over MgSO4 and concentrated. The residue was chromotographed on a silica gel column, eluting with methylene chloride:methanol 100:4 to afford to give the free base of the title compound (72.5 mg, 66% yield). MS (DCI/NH3) m/z 335 (M+H)+. 1H NMR (CDCl3, 300 MHz) δ1.10 (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 ether/THF to give the title compound. mp 194° C. (dec). MS (DCI/NH3) m/z 335 (M+H)+. 1 H 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).

Workup

  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. washeluting with methylene chloride:methanol 100:4
  7. customto afford

Sources & evidence

ORD record
ord-24ada19dba7c49c6a5f261496dd8d30d
Source dataset
uspto-grants-1997_05
Patent number
US05629325

Reaction notes

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