Acetic Acid → HCID 17980102, compound

HRID 1766233Notes

Reaction equation

HRID 1766233 reaction equation
[F:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:11]3[CH2:12][CH2:13][N:14]([CH3:17])[CH2:15][CH:16]=3)=[CH:7][NH:8]2)=[CH:4][C:3]=1[O:18][CH3:19].[BH4-].[Na+].C(O)(=O)C.Cl.[OH-].[Na+]>O1CCCC1>[F:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([CH:11]3[CH2:16][CH2:15][N:14]([CH3:17])[CH2:13][CH2:12]3)=[CH:7][NH:8]2)=[CH:4][C:3]=1[O:18][CH3:19]

Participants

7

Reactant 5

HCID 176Acetic AcidHCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 4311764Sodium borohydrideHCID 17980100HCID 17980100, compound

Product 1

HCID 17980102HCID 17980102, compoundYield 82%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A suspension of 6-fluoro-5-methoxy-3-(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-indole (15.7 mmole, 4.09 g) in tetrahydrofuran (30 mL) at room temperature was added sodium borohydride (31.4 mmole, 1.19 g). To this suspension was carefully added acetic acid (47.1 mmole, 2.83 g). Severe frothing occurred during the addition. The reaction was stirred at room temperature for 1.0 hours. To the heavy suspension was added 5N hydrochloric acid (30 mL). The resulting solution was stirred at room temperature for 1.0 hour. Reaction was reduced in volume, cooled to 0° C. and the pH was adjusted to >12 with 50% wt/wt sodium hydroxide. The reaction was extracted with ethyl acetate (3×25 mL), organic phases were combined, dried over sodium sulfate, filtered and concentrated in vacuo to a solid. The resulting material was subjected to Waters LC2000 normal phase chromatography, eluting with a linear gradient of 0 to 10% methanol containing 1% ammonium hydroxide:chloroform over a thirty minute period collecting 150 mL fractions. Fractions containing the title compound were combined, reduced in volume and set aside. The resulting crystals were collected by filtration to afford 2.30 g (82%) of the title compound: mass spectrum (ion spray): m/z=263 (M+1); 1H NMR (DMSOd6): 10.65 (s, 1H), 7.16 (d, 1H), 7.13 (d, 1H), 7.03 (d, 1H), 3.83 (s, 3H), 2.81 (m, 2H), 2.63 (m, 1H), 2.20 (s, 3H), 1.98 (m, 2H), 1.86 (m, 2H), 1.62 (m, 2H); Calculated for C15H19FN2O: C, 68.21; H, 7.33; N, 6.66. Found: C, 68.09; H, 6.95; N, 10.52.

Workup

  1. additionSevere frothing occurred during the addition
  2. stirringThe resulting solution was stirred at room temperature for 1.0 hour
  3. customReaction
  4. temperaturecooled to 0° C.
  5. extractionThe reaction was extracted with ethyl acetate (3×25 mL), organic phases
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo to a solid
  9. washeluting with a linear gradient of 0 to 10% methanol containing 1% ammonium hydroxide
  10. customchloroform over a thirty minute period collecting 150 mL fractions
  11. additionFractions containing the title compound
  12. filtrationThe resulting crystals were collected by filtration

Sources & evidence

ORD record
ord-5c779b9adfb348789a690e98fc56b418
Source dataset
uspto-grants-2007_06
Patent number
US07230011B2

Reaction notes

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