Trifluoroacetic acid → HCID 69204264, compound

HRID 28489Notes

Reaction equation

HRID 28489 reaction equation
[CH:1]([N:14]1[CH2:17][CH:16]([CH:18](OC)[C:19]2[C:27]3[C:22](=[CH:23][CH:24]=[C:25]([C:28]#[N:29])[CH:26]=3)[NH:21][CH:20]=2)[CH2:15]1)([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C([SiH](CC)CC)C.FC(F)(F)C(O)=O.[OH-].[NH4+]>C(Cl)Cl>[CH:1]([N:14]1[CH2:15][CH:16]([CH2:18][C:19]2[C:27]3[C:22](=[CH:23][CH:24]=[C:25]([C:28]#[N:29])[CH:26]=3)[NH:21][CH:20]=2)[CH2:17]1)([C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1)[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1

Participants

6

Reactant 4

HCID 6422Trifluoroacetic acidHCID 12052TriethylsilaneHCID 14923Ammonium HydroxideHCID 21892099HCID 21892099, compound

Product 1

HCID 69204264HCID 69204264, compoundYield 86%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of 3-[(1-benzhydryl-azetidin-3-yl)-methoxy-methyl]-1H-indole-5-carbonitrile, triethylsilane (5.5 ml, 34 mmol) and trifluoroacetic acid (6.6 mL, 86 mmol) in methylene chloride (40 mL) was refluxed overnight. The reaction was poured into ice and neutralized with concentrated ammonium hydroxide. The mixture was extracted with methylene chloride (3×100 mL). The organic layer was washed with water (3×80 mL), dried over anhydrous sodium sulfate, filtered and solvent removed under vacuum. The crude oil was column chromatographed on a Biotage (40% ethyl acetate-hexane/hexane). The product-containing fractions were concentrated under vacuum to give 0.56 g (86%) of the title compound as a clear oil. MS ES m/e 378 (M+H)+; 1H NMR (500 MHz, DMSO-D6): 2.74-2.78 δ (M, 3H), 2.96 δ (d J=6.7 Hz, 2H), 3.21 δ (t, J=6.4 Hz, 2H), 4.4 δ (s, 1H), 7.15-7.17 δ (m, 2H), 7.24-7.29 δ (m, 5H), 7.38-7.418 δ (m, 5H), 7.47 δ (d, J=8.4 Hz, 1H), 8.07 δ (s, 1H), 11.37 δ (br, 1H).

Workup

  1. extractionThe mixture was extracted with methylene chloride (3×100 mL)
  2. washThe organic layer was washed with water (3×80 mL)
  3. dry with materialdried over anhydrous sodium sulfate
  4. filtrationfiltered
  5. customsolvent removed under vacuum
  6. customchromatographed on a Biotage (40% ethyl acetate-hexane/hexane)
  7. concentrationThe product-containing fractions were concentrated under vacuum

Sources & evidence

ORD record
ord-956bbfda1d814feba6199bef47a81d58
Source dataset
uspto-grants-2008_09
Patent number
US07419986B2

Reaction notes

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