Formaldehyde → (1-Benzylindazol-3-yl)methanol

HRID 1803403Notes

Reaction equation

HRID 1803403 reaction equation
C([Mg]Cl)(C)C.[CH2:6]([N:13]1[C:21]2[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=2)[C:15](Br)=[N:14]1)[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1.[CH2:23]=[O:24].OP(O)(O)=O>C1COCC1.C1(C)C(C)=CC=CC=1>[CH2:6]([N:13]1[C:21]2[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=2)[C:15]([CH2:23][OH:24])=[N:14]1)[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1

Participants

7

Reactant 4

HCID 712Formaldehyde2×HCID 1004Phosphoric AcidHCID 128082101-benzyl-3-bromo-1H-indazoleHCID 178418918HCID 178418918, compound

Product 1

HCID 10657568(1-Benzylindazol-3-yl)methanolYield 34%

Reagents, catalysts & solvents 2

HCID 7237O-XyleneSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-10 °C

Procedure

A solution of 2M i-PrMgCl in THF (69 mL, 138 mmol, 4.0 eq.) was added to a suitably thoroughly dried flask maintained under a nitrogen atmosphere. The solution was cooled to approximately −10° C. A solution of 1-benzyl-3-bromo-1H-indazole (10 g, 34.8 mmol, 1.0 eq.) in anhydrous THF (40 mL) was added over approximately one hour keeping the temperature constant. The reaction mixture was kept stirred for at least 6 hours, and a yellow suspension was obtained. Gaseous formaldehyde (generated by heating a suspension of 16.7 g of paraformaldehyde in 60 mL of xylene at approximately 115° C.) was passed over this for approximately two hours at a temperature of below 0° C. When the reaction was complete, dilute H3PO4 was added and the excess of re-polymerised paraformaldehyde was removed by filtration. Me-THF (60 mL) was added to the mixture and the phases were separated. The organic phase was washed with a dilute solution of NaHCO3. After concentration of the organic phase an oily residue containing the product was obtained. Subsequent purification of the crude product by silica gel chromatography yielded 2.8 g of white solid (yield: 34%).

Workup

  1. temperaturemaintained under a nitrogen atmosphere
  2. customa yellow suspension was obtained
  3. temperatureby heating
  4. customfor approximately two hours
  5. customat a temperature of below 0° C
  6. customthe excess of re-polymerised paraformaldehyde was removed by filtration
  7. additionMe-THF (60 mL) was added to the mixture
  8. customthe phases were separated
  9. washThe organic phase was washed with a dilute solution of NaHCO3
  10. additionAfter concentration of the organic phase an oily residue containing the product
  11. customwas obtained
  12. customSubsequent purification of the crude product by silica gel chromatography

Sources & evidence

ORD record
ord-23de0ee39ab641a2a4df5264bff4241e
Source dataset
uspto-grants-2013_01
Patent number
US08350052B2

Reaction notes

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