Sodium Sulfate → HCID 21071625, compound

HRID 1371940Notes

Reaction equation

HRID 1371940 reaction equation
[F:1][C:2]1[CH:10]=[CH:9][C:8]([F:11])=[C:7]2[C:3]=1[C:4]([CH2:12][CH2:13][NH2:14])=[CH:5][NH:6]2.[F:15][C:16]([F:28])([F:27])[CH2:17][O:18][C:19]1[CH:20]=[C:21]([CH:24]=[CH:25][CH:26]=1)[CH:22]=O.S([O-])([O-])(=O)=O.[Na+].[Na+].[BH4-].[Na+]>C(O)(=O)C.C(O)C>[F:1][C:2]1[CH:10]=[CH:9][C:8]([F:11])=[C:7]2[C:3]=1[C:4]([CH2:12][CH2:13][NH:14][CH2:22][C:21]1[CH:24]=[CH:25][CH:26]=[C:19]([O:18][CH2:17][C:16]([F:15])([F:27])[F:28])[CH:20]=1)=[CH:5][NH:6]2

Participants

7

Reactant 4

HCID 24436Sodium SulfateHCID 4311764Sodium borohydrideHCID 47709473-(2,2,2-Trifluoroethoxy)benzaldehydeHCID 21071419HCID 21071419, compound

Product 1

HCID 21071625HCID 21071625, compound

Reagents, catalysts & solvents 2

HCID 176Acetic AcidCatalystHCID 702EthanolSolvent

Conditions

Temperature
70 °C

Procedure

Combine 2-(4,7-difluoro-1H-indol-3-yl)ethylamine (483 mg, 2.46 mmol) and ethanol (45 mL) and stir. After 10 minutes treat with 3-(2,2,2-trifluoroethoxy)benzaldehyde (502 mg, 2.46 mmol) and anhydrous sodium sulfate (3.5 g) and stir under nitrogen and heat at 70° C. After 2 h., cool the reaction vacuum filter to remove the sodium sulfate and treat with sodium borohydride (279 mg, 7.38 mmol) in a 500 mL round bottom flask equipped with magnetic stirring. Allow the solution to stir for 2 hours at room temperature and then carefully treat with three drops of glacial acetic acid to quench the excess hydride. Remove the solvent in vacuo and re-dissolve the crude material in methanol. Purify by a 10 g SCX column by washing thoroughly with methanol, eluting with 2N ammonia in methanol, and concentrating in vacuo to give the title compound as a straw colored oil. Prepare the hydrochloride salt by dissolving the free base (800 mg, 2.08 mmol) in methanol (15 mL) and treating with a solution of ammonium chloride (111 mg, 2.08 mmol) in methanol (5 mL). Sonicate the mixture for 10 minutes before concentrating in vacuo to give a white solid. Recrystallize from ethyl acetate to obtain the hydrochloride salt of the title compound: mp 208.5–210.0° C.; 1H NMR (400 MHz, dmso-d6): 11.79 (br s, 1H), 9.21 (br s, 2H), 7.39 (t, 1H, J=7.8 Hz), 7.32 (d, 1H, J=2.0 Hz) 7.30 (s, 1H), 7.18 (d, 1H, J=8.0 Hz), 7.11 (dd, 1H, J=2.6, 8.2 Hz), 6.85–6.91 (m, 1H), 6.67–6.73 (m, 1H), 4.77 (q, 2H, J=8.8 Hz), 4.16 (s, 4H), 3.12–3.16 (m, 4H); MS (APCI): m/e 385.1 (M+1); CHN (for C19H17F5N2O.HCl) calcd: C, 54.23, H 4.31, N, 6.66; found: C, 54.20, H 4.30, N 6.66.

Workup

  1. temperaturecool
  2. customthe reaction vacuum
  3. filtrationfilter
  4. customto remove the sodium sulfate
  5. customequipped with magnetic stirring
  6. stirringto stir for 2 hours at room temperature
  7. customto quench the excess hydride
  8. customRemove the solvent in vacuo
  9. dissolutionre-dissolve the crude material in methanol
  10. customPurify by a 10 g SCX column
  11. washby washing thoroughly with methanol
  12. washeluting with 2N ammonia in methanol
  13. concentrationconcentrating in vacuo

Sources & evidence

ORD record
ord-f00a35d29732456b8bd469499ae09038
Source dataset
uspto-grants-2007_01
Patent number
US07157488B2

Reaction notes

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