Formaldehyde → HCID 70027169, compound

HRID 1264235Notes

Reaction equation

HRID 1264235 reaction equation
C(O[C:6]([NH:8][CH2:9][C:10]1[CH:15]=[C:14]([C:16]2[CH:25]=[CH:24][C:19]([C:20]([O:22][CH3:23])=[O:21])=[CH:18][CH:17]=2)[CH:13]=[CH:12][N:11]=1)=O)(C)(C)C.[C:26](O)(C(F)(F)F)=O.C=O>C(Cl)Cl.O>[CH3:26][N:8]([CH2:9][C:10]1[CH:15]=[C:14]([C:16]2[CH:17]=[CH:18][C:19]([C:20]([O:22][CH3:23])=[O:21])=[CH:24][CH:25]=2)[CH:13]=[CH:12][N:11]=1)[CH3:6]

Participants

6

Reactant 3

HCID 712FormaldehydeHCID 6422Trifluoroacetic acid2×HCID 18617752HCID 18617752, compound

Product 1

HCID 70027169HCID 70027169, compound

Reagents, catalysts & solvents 2

HCID 962WaterCatalystHCID 6344DichloromethaneSolvent

Procedure

To a solution of Methyl 4-(2-[t-butyloxycarbonylamino-methyl]-pyridin-4-yl)-benzoate (reference example 56) (520 mg, 1.5 mmol) in CH2Cl2 (5 mL) is added TFA (1.5 mL) and 2 drops of water (approx. 100 mL). The resulting solution is stirred for 90 minutes, then concentrated under reduced pressure. The residue is dissolved in THF (4 mL) then NaBH4 added (222 mg, 6 mmol) followed by paraformaldehyde (360 mg, 12 mmol). To this mixture is added TFA (4 mL) dropwise. The resulting mixture is stirred for 6 hours then concentrated. The residue is brought to pH 8 with aqueous NaOH (1M) and sat NaHCO3. The mixture is then extracted with ethyl acetate then ethyl acetate methanol (9/1). The combined organic extracts are washed with brine dried over MgSO4 and concentrated. The residue is purified by flash chromatography (eluting with 10% methanol in CH2Cl2) to give 329 mg of the title compound. 1H NMR (CD3OD) δ 3.00 (s, 6H), 3.94 (s, 3H), 4.56 (s, 2H), 7.74 (d, J=5 Hz, 1H), 7.83 (s, 1H), 7.88 (d, J=8 Hz, 2H), 8.17 (d, J=8 Hz, 2H), 8.76 (d, J=5 Hz, 1H). MS (ion spray) m/z 271 (M+H).

Workup

  1. concentrationconcentrated under reduced pressure
  2. dissolutionThe residue is dissolved in THF (4 mL)
  3. additionNaBH4 added (222 mg, 6 mmol)
  4. stirringThe resulting mixture is stirred for 6 hours
  5. concentrationthen concentrated
  6. extractionThe mixture is then extracted with ethyl acetate
  7. washThe combined organic extracts are washed with brine
  8. dry with materialdried over MgSO4
  9. concentrationconcentrated
  10. customThe residue is purified by flash chromatography (eluting with 10% methanol in CH2Cl2)

Sources & evidence

ORD record
ord-c7f345dc037c4b0b8422a83ddf67a1c7
Source dataset
uspto-grants-2003_04
Patent number
US06541505B1

Reaction notes

Loading…