Dimethylamine → 6-Fluorogramine

HRID 1666876Notes

Reaction equation

HRID 1666876 reaction equation
[CH3:1][NH:2][CH3:3].[CH2:4]=O.[F:6][C:7]1[CH:15]=[C:14]2[C:10]([CH:11]=[CH:12][NH:13]2)=[CH:9][CH:8]=1.[OH-].[Na+]>C(O)(=O)C>[CH3:1][N:2]([CH2:4][C:11]1[C:10]2[C:14](=[CH:15][C:7]([F:6])=[CH:8][CH:9]=2)[NH:13][CH:12]=1)[CH3:3]

Participants

6

Reactant 4

HCID 674DimethylamineHCID 712FormaldehydeHCID 14798Sodium HydroxideHCID 3512786-Fluoroindole

Product 1

HCID 27744716-Fluorogramine

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Conditions

Temperature
0 °C

Procedure

Add dropwise 422 mL of glacial acetic acid to 40% aqueous dimethylamine (408 mL) over 40 minutes while maintaining the temperature below about 15° C. Cool to 0° C. After stirring for 20 minutes at 0° C., slowly add 37% aqueous formaldehyde (289 mL, 1.3 eq.) over about 15 minutes. Add 6-fluoroindole (400 g, 2.96 mol, 1 eq.) in four portions over about 15 minutes. After 30 minutes, divide the reaction mixture into two portions. To one portion, slowly 1149 g (75% of total mass) over 30 minutes to 3 L of 10% NaOH and stir at room temperature. After 18 hours, collect the solid that forms, wash three times with 200 mL of water, dry by suction to give wet 3-(N,N-dimethylaminomethyl)-6-fluoroindole.

Workup

  1. temperaturewhile maintaining the temperature below about 15° C
  2. waitAfter 30 minutes
  3. waitAfter 18 hours
  4. customcollect the solid that forms
  5. washwash three times with 200 mL of water
  6. customdry by suction

Sources & evidence

ORD record
ord-6288e7f756ac49558a12bc5ce2124abc
Source dataset
uspto-grants-2011_10
Patent number
US08044090B2

Reaction notes

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