Formaldehyde → HCID 21868725, compound

HRID 857462Notes

Reaction equation

HRID 857462 reaction equation
[CH2:1]=O.ClC1[C:12](F)=[C:11]2[C:7]([CH:8]=[CH:9][N:10]2[CH2:14][CH2:15][NH2:16])=CC=1.S([O-])([O-])(=O)=O.[Mg+2].[F:23][C:24](F)(F)[C:25](O)=O.C(=O)([O-])O.[Na+].Cl[CH2:36][Cl:37]>>[Cl:37][C:36]1[C:24]([F:23])=[CH:25][C:7]2[CH:8]=[C:9]3[CH2:1][NH:16][CH2:15][CH2:14][N:10]3[C:11]=2[CH:12]=1

Participants

7

Reactant 6

HCID 712FormaldehydeHCID 6344Dichloromethane2×HCID 6422Trifluoroacetic acidHCID 24083Sulfuric acid magnesium salt (1:1)HCID 516892Sodium BicarbonateHCID 69606927HCID 69606927, compound

Product 1

HCID 21868725HCID 21868725, compound

Procedure

Paraformaldehyde (0.95 g, 30 mmol) was added in 1 portion to a stirred solution of 1-(6-chloro-7-fluoroindol-1-yl)-2-ethylamine (1.3 g, 6.1 mmol) and magnesium sulfate (1.5 g) in dichloromethane (15 mL) at room temperature under Ar. The reaction was stirred at room temperature for 4 h then filtered. The filter-cake was washed with dichloromethane (50 mL) and the filtrate was concentrated under vacuum to leave a crude oil. The oil was dissolved in dichloromethane (10 mL) and trifluoroacetic acid (2 mL) was added. The reaction was stirred at room temperature under Ar for 10 min then basified by pouring into saturated aqueous sodium hydrogen carbonate solution (100 mL). The mixture was extracted with ethyl acetate (3×80 mL) and the combined organic extracts were washed with brine (1×80 mL), dried (magnesium sulfuric), filtered and the solvent removed under vacuum to leave a crude oil. The oil was purified by flash column chromatography [SiO2; ethyl acetate-methanol-ammonium hydroxide (9:1:0)→(90:9:1)] to give the product as a yellow oil that crystallised on standing (0.32 g, 23%). NMR δH (400 MHz; CDCl3) 7.25–7.27 (2H, m), 6.14 (1H, s), 4.20 (2H, s), 3.95 (2H, t, J 5.5 Hz), 3.35 (2H, t, J 5.5 Hz).

Workup

  1. filtrationthen filtered
  2. washThe filter-cake was washed with dichloromethane (50 mL)
  3. concentrationthe filtrate was concentrated under vacuum
  4. customto leave a crude oil
  5. stirringThe reaction was stirred at room temperature under Ar for 10 min
  6. extractionThe mixture was extracted with ethyl acetate (3×80 mL)
  7. washthe combined organic extracts were washed with brine (1×80 mL)
  8. dry with materialdried (magnesium sulfuric)
  9. filtrationfiltered
  10. customthe solvent removed under vacuum
  11. customto leave a crude oil
  12. customThe oil was purified by flash column chromatography [SiO2; ethyl acetate-methanol-ammonium hydroxide (9:1:0)→(90:9:1)]

Sources & evidence

ORD record
ord-32170897afe14f1ea35a763f3d065b33
Source dataset
uspto-grants-2006_12
Patent number
US07145009B2

Reaction notes

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