Trifluoroacetic acid → HCID 68108521, compound

HRID 2179438Notes

Reaction equation

HRID 2179438 reaction equation
[Cl:1][C:2]1[C:7]2[O:8][C:9]3[CH2:14][CH2:13][N:12](C(OC(C)(C)C)=O)[CH2:11][C:10]=3[C:6]=2[CH:5]=[C:4]([CH:22]([OH:29])[C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[CH:3]=1.FC(F)(F)C(O)=O>ClCCl>[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:22]([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[OH:29])[CH:3]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 68109410HCID 68109410, compound

Product 1

HCID 68108521HCID 68108521, compoundYield 85.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of the product of step A (50.0 mg, 0.12 mmol) in dichloromethane (4 mL) was added trifluoroacetic acid (0.4 mL). After stirring for 2 h at ambient temperature the reaction mixture was quenched with 10% sodium bicarbonate solution (15 mL) and extracted with dichloromethane. The organic extract was 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-1,2,3,4-tetrahydrobenzofuro[3,2-c]pyridin-8-yl)(phenyl)methanol hydrochloride (18 mg, 47%, AUC HPLC 97.1%) as a white solid: mp 260° C. dec.; 1H NMR (CD3OD, 300 MHz) δ 7.46 (s, 1H), 7.41-7.20 (m, 6H), 5.85 (br s, 1H), 4.40 (s, 2H), 3.68 (t, J=6 Hz, 2H), 3.25-3.15 (m, 2H); APCI MS m/z 314 [M+H]+.

Workup

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

Sources & evidence

ORD record
ord-e83af55d4b924e2289e59ffc21e5b9e7
Source dataset
uspto-grants-2015_06
Patent number
US09067949B2

Reaction notes

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