Trifluoroacetic acid → HCID 68108969, compound

HRID 2179440Notes

Reaction equation

HRID 2179440 reaction equation
[Cl:1][C:2]1[C:7]2[O:8][C:9]3[CH2:14][CH2:13][NH:12][CH2:11][C:10]=3[C:6]=2[CH:5]=[C:4]([C:15]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)=[CH2:16])[CH:3]=1.C([SiH](CC)CC)C.FC(F)(F)C(O)=O>>[ClH:1].[Cl:1][C:2]1[C:7]2[O:8][C:9]3[CH2:14][CH2:13][NH:12][CH2:11][C:10]=3[C:6]=2[CH:5]=[C:4]([CH:15]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[CH3:16])[CH:3]=1

Participants

4

Reactant 3

HCID 6422Trifluoroacetic acidHCID 12052TriethylsilaneHCID 68109725HCID 68109725, compound

Product 1

HCID 68108969HCID 68108969, compoundYield 153.1%

Procedure

To the product obtained in step B (40.0 mg, 0.12 mmol) was added triethylsilane (0.5 mL, 3.22 mmol), trifluoroacetic acid (0.35 mL, 4.51 mmol) and boron trifluoride-diethylether complex (0.65 mL, 4.51 mmol) at 0° C. The reaction mixture was stirred at ambient temperature for 24 h under a nitrogen atmosphere, quenched with 20% potassium carbonate solution (15 mL) and extracted with dichloromethane. The organic extract was washed with water followed by brine, dried over sodium sulphate and concentrated in vacuo. The residue was purified by flash column chromatography (SiO2, 9:1 dichloromethane/methanol). The product was converted to hydrochloride salt by dissolving in dichloromethane and treating with 2 M HCl in diethyl ether at 0° C. After stirring for 20 min the reaction mixture was concentrated in vacuo to give 6-chloro-8-(1-phenylethyl)-1,2,3,4-tetrahydrobenzofuro[3,2-c]pyridine hydrochloride (32 mg, 90%, AUC HPLC 96.5%) as an off-white solid: mp 245-255° C. dec.; 1H NMR (CD3OD, 400 MHz) δ 7.38 (d, J=0.8 Hz, 1H), 7.31-7.20 (m, 5H), 7.20-7.14 (m, 1H), 4.39 (s, 2H), 4.27 (q, J=7.2 Hz, 1H), 3.67 (t, J=6.0 Hz, 2H), 3.18 (t, J=6.0 Hz, 2H), 1.67 (d, J=7.2 Hz, 3H); APCI MS m/z 312 [M+H]+

Workup

  1. customquenched with 20% potassium carbonate solution (15 mL)
  2. extractionextracted with dichloromethane
  3. extractionThe organic extract
  4. washwas washed with water
  5. dry with materialdried over sodium sulphate
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by flash column chromatography (SiO2, 9:1 dichloromethane/methanol)
  8. dissolutionby dissolving in dichloromethane
  9. additiontreating with 2 M HCl in diethyl ether at 0° C
  10. stirringAfter stirring for 20 min the reaction mixture
  11. concentrationwas concentrated in vacuo

Sources & evidence

ORD record
ord-6c5a49359a52435b8b60295106a1b02c
Source dataset
uspto-grants-2015_06
Patent number
US09067949B2

Reaction notes

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