Trifluoroacetic acid → HCID 66654431, compound

HRID 2036193Notes

Reaction equation

HRID 2036193 reaction equation
FC(F)(F)C(O)=O.C([O:12][C:13]([N:15]1[CH2:24][C:23]([CH3:26])([CH3:25])[C:22]2[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=2)[CH:16]1[C:27]1[CH:32]=[C:31]([Cl:33])[CH:30]=[CH:29][C:28]=1[O:34][CH2:35][C:36]([O:38]CC)=[O:37])=[O:14])(C)(C)C.C(N(CC)CC)C.ClC(O[CH2:52][C:53]1[CH:58]=[CH:57][CH:56]=[CH:55][CH:54]=1)=O>C(Cl)Cl>[CH2:52]([O:12][C:13]([N:15]1[CH2:24][C:23]([CH3:26])([CH3:25])[C:18]2[C:17](=[CH:22][CH:21]=[CH:20][CH:19]=2)[CH:16]1[C:27]1[CH:32]=[C:31]([Cl:33])[CH:30]=[CH:29][C:28]=1[O:34][CH2:35][C:36]([OH:38])=[O:37])=[O:14])[C:53]1[CH:58]=[CH:57][CH:56]=[CH:55][CH:54]=1

Participants

6

Reactant 4

HCID 6422Trifluoroacetic acidHCID 8471TriethylamineHCID 10387Benzyl chloroformateHCID 66654423HCID 66654423, compound

Product 1

HCID 66654431HCID 66654431, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

Trifluoroacetic acid (0.92 mL, 11.8 mmol, 20.0 eq.) was added to a solution of (±)-1-(5-chloro-2-ethoxycarbonylmethoxy-phenyl)-4,4-dimethyl-3,4-dihydro-1H-isoquinoline-2-carboxylic acid tert-butyl ester (280 mg, 0.59 mmol, 1.0 eq.) in DCM (1 mL). The resulting mixture was stirred at r.t. during 5 hours. The mixture was concentrated in vacuo. To an-ice cooled suspension of the residue and triethylamine (0.41 mL, 2.95 mmol, 5.0 eq.) in DCM (1 mL), benzyl chloroformate (0.18 mL, 1.18 mmol, 2.0 eq.) was added dropwise. Upon completion of the addition, the cooling bath was removed and the suspension was stirred at r.t. for 18 hours. The reaction was quenched with 1M aq. citric acid soln. (5 mL). The layers were separated. The aq. phase was extracted with DCM (3×2 mL). The comb. org. phases were dried over MgSO4 and concentrated in vacuo. The residue was dissolved in DMF (1 mL), 1M aq. NaOH soln. (1 mL) was added. The resulting solution was stirred at r.t. for 18 hours. The solution was neutralized with formic acid (1 mL), filtered, and then purified by prep. HPLC (column: Atlantis, 30×75 mm, 10 um, UV/MS, acidic conditions) and concentrated in vacuo to give the desired acid.

Workup

  1. concentrationThe mixture was concentrated in vacuo
  2. temperatureTo an-ice cooled
  3. additionwas added dropwise
  4. additionUpon completion of the addition
  5. customthe cooling bath was removed
  6. stirringthe suspension was stirred at r.t. for 18 hours
  7. customThe reaction was quenched with 1M aq. citric acid soln
  8. customThe layers were separated
  9. extractionThe aq. phase was extracted with DCM (3×2 mL)
  10. dry with materialphases were dried over MgSO4
  11. concentrationconcentrated in vacuo
  12. dissolutionThe residue was dissolved in DMF (1 mL)
  13. addition(1 mL) was added
  14. stirringThe resulting solution was stirred at r.t. for 18 hours
  15. filtrationfiltered
  16. custompurified by prep
  17. concentrationHPLC (column: Atlantis, 30×75 mm, 10 um, UV/MS, acidic conditions) and concentrated in vacuo

Sources & evidence

ORD record
ord-dcd329d8c60d4b399ae152e72713a8f7
Source dataset
uspto-grants-2013_11
Patent number
US08575158B2

Reaction notes

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