Trifluoroacetic acid → HCID 54343518, compound

HRID 445382Notes

Reaction equation

HRID 445382 reaction equation
[Cl:1][C:2]1[N:7]=[CH:6][C:5]([CH:8]2[C:17]3[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=3)[CH2:11][CH2:10][N:9]2C(OCC2C=CC=CC=2)=O)=[CH:4][CH:3]=1.C(O)(C(F)(F)F)=O>C(Cl)Cl>[Cl:1][C:2]1[N:7]=[CH:6][C:5]([CH:8]2[C:17]3[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=3)[CH2:11][CH2:10][NH:9]2)=[CH:4][CH:3]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 59536305HCID 59536305, compound

Product 1

HCID 54343518HCID 54343518, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a round-bottomed flask was added crude benzyl 1-(6-chloropyridin-3-yl)-3,4-dihydroisoquinoline-2(1H)-carboxylate (170 mg, 449 μmol), CH2Cl2 (10 mL) and TFA (10 mL). The reaction was allowed to stir at RT. After 3 days, LC-MS shows little progress. The reaction was concentrated in vacuo to remove CH2Cl2 and the resulting solution allowed to stir for another 3 days, then cautiously poured into 10% Na2CO3 and extracted with CH2Cl2 (3×20 mL). The combined organic layers were concentrated in vacuo and purified by reverse-phase preparative HPLC (Shimadzu) on a Phenomenex Gemini® column (5 micron, C18, 110 Å, Axia, 100×50 mm) eluting at 90 mL/min with an linear gradient of 10% to 100% MeCN (0.1% TFA) in water (0.1% TFA) over 20 min to give crude 1-(6-chloropyridin-3-yl)-1,2,3,4-tetrahydroisoquinoline as a white solid. The crude solid was carried into the next step. MS (ESI pos. ion) m/z: 245 (M+1).

Workup

  1. concentrationThe reaction was concentrated in vacuo
  2. customto remove CH2Cl2
  3. stirringto stir for another 3 days
  4. additioncautiously poured into 10% Na2CO3
  5. extractionextracted with CH2Cl2 (3×20 mL)
  6. concentrationThe combined organic layers were concentrated in vacuo
  7. custompurified by reverse-phase preparative HPLC (Shimadzu) on a Phenomenex Gemini® column (5 micron, C18, 110 Å, Axia, 100×50 mm)
  8. washeluting at 90 mL/min with an linear gradient of 10% to 100% MeCN (0.1% TFA) in water (0.1% TFA) over 20 min

Sources & evidence

ORD record
ord-f31a234be12d40b7a55acdf2951ed59c
Source dataset
uspto-grants-2013_07
Patent number
US08476297B2

Reaction notes

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