Formaldehyde → HCID 18425821, compound

HRID 1280718Notes

Reaction equation

HRID 1280718 reaction equation
F[C:2](F)(F)[C:3](O)=O.[NH:8]1[CH2:12][CH2:11][CH:10]([S:13]([C:16]2[CH:21]=[CH:20][C:19]([OH:22])=[CH:18][CH:17]=2)(=[O:15])=[O:14])[CH2:9]1.C([O-])(O)=O.[Na+].C=O.[C:30]1([CH2:36][C:37]#C)[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1>CO.Cl[Cu]>[C:30]1([CH2:36][C:37]#[C:2][CH2:3][N:8]2[CH2:12][CH2:11][CH:10]([S:13]([C:16]3[CH:21]=[CH:20][C:19]([OH:22])=[CH:18][CH:17]=3)(=[O:15])=[O:14])[CH2:9]2)[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1

Participants

7

Reactant 4

HCID 712FormaldehydeHCID 516892Sodium BicarbonateHCID 575753BenzylacetyleneHCID 18425771(RS)-4-(Pyrrolidine-3-sulfonyl)-phenol trifluoroacetic acid

Product 1

HCID 18425821HCID 18425821, compoundYield 69%

Reagents, catalysts & solvents 2

HCID 62652Cuprous chlorideCatalystHCID 887MethanolSolvent

Conditions

Temperature
100 °C

Procedure

(RS)-4-(Pyrrolidine-3-sulfonyl)-phenol trifluoro-acetic acid (0.2 g, 0.59 mmol) and NaHCO3 (74 mg, 0.88 mmol) were suspended in MeOH (2 ml). After 10 minutes, reaction mixture was concentrated. The residue was taken up in CHCl3. The resulting solid was filtered and the filtrate was concentrated. The so-obtained foam was dissolved in dioxane (2 ml) and treated successively with paraformaldehyde (17.6 mg, 0.586 mmol), 3-phenyl-1-propyne (68 mg, 0.586 mmol) and CuCl (6.2 mg, 0.062 mmol). The reaction mixture was stirred at 100° C. for 0.75 hour then cooled to room temperature and concentrated. The residue was treated with saturated NaHCO3. The aqueous phase was extracted with CH2Cl2 (3 times). The combined organic phases were dried over Na2SO4, filtered and the solvent was evaporated. The residue was chromatographed over silica gel (CH2Cl2—MeOH 19:1) to provide (RS)-4-[l-(4-phenyl-but-2-ynyl)-pyrrolidine-3-sulfonyl]-phenol (0.14 g, 69%) as an orange foam, MS: m/e=356.3 (M+H+).

Workup

  1. customreaction mixture
  2. concentrationwas concentrated
  3. filtrationThe resulting solid was filtered
  4. concentrationthe filtrate was concentrated
  5. dissolutionThe so-obtained foam was dissolved in dioxane (2 ml)
  6. temperaturethen cooled to room temperature
  7. concentrationconcentrated
  8. additionThe residue was treated with saturated NaHCO3
  9. extractionThe aqueous phase was extracted with CH2Cl2 (3 times)
  10. dry with materialThe combined organic phases were dried over Na2SO4
  11. filtrationfiltered
  12. customthe solvent was evaporated
  13. customThe residue was chromatographed over silica gel (CH2Cl2—MeOH 19:1)

Sources & evidence

ORD record
ord-9b0afdbcbe6f4131adacc47e470428b4
Source dataset
uspto-grants-2002_09
Patent number
US06451819B2

Reaction notes

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