(+/-)-1-(5-chloro-2-ethoxycarbonylmethoxy-phenyl)-3,4-dihydro-1H-isoquinoline-2-carboxylic acid tert-butyl ester → (+/-)-[2-(1,2,3,4-Tetrahydro-isoquinolin-1-yl)-phenoxy]-acetic acid ethyl ester

HRID 2036222Notes

Reaction equation

HRID 2036222 reaction equation
C(OC([N:8]1[CH2:17][CH2:16][C:15]2[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=2)[CH:9]1[C:18]1[CH:23]=[C:22](Cl)[CH:21]=[CH:20][C:19]=1[O:25][CH2:26][C:27]([O:29][CH2:30][CH3:31])=[O:28])=O)(C)(C)C>CCO.[Pd]>[CH2:30]([O:29][C:27](=[O:28])[CH2:26][O:25][C:19]1[CH:20]=[CH:21][CH:22]=[CH:23][C:18]=1[CH:9]1[C:10]2[C:15](=[CH:14][CH:13]=[CH:12][CH:11]=2)[CH2:16][CH2:17][NH:8]1)[CH3:31]

Participants

4

Reactant 1

HCID 66654193(+/-)-1-(5-chloro-2-ethoxycarbonylmethoxy-phenyl)-3,4-dihydro-1H-isoquinoline-2-carboxylic acid tert-butyl ester

Product 1

HCID 89523813(+/-)-[2-(1,2,3,4-Tetrahydro-isoquinolin-1-yl)-phenoxy]-acetic acid ethyl ester

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 702EthanolSolvent

Conditions

Temperature
50 °C

Procedure

To a solution of (±)-1-(5-chloro-2-ethoxycarbonylmethoxy-phenyl)-3,4-dihydro-1H-isoquinoline-2-carboxylic acid tert-butyl ester (446 mg, 1.0 mmol, 1.0 eq.) in EtOH (4.8 mL) under N2, palladium on activated carbon (10 wt. %, 106 mg) was added. The flask was carefully evacuated and refilled with H2 (3×). The black suspension was stirred at 50° C. under an H2-atmosphere for 48 hours. The black suspension was filtered through Celite. The Celite was rinsed with EtOH. The filtrate was concentrated in vacuo. To an ice-cooled solution of the residue in DCM (1.8 mL), 4M HCl in dioxane (2.6 mL) was added. The resulting solution was stirred at r.t. for 18 hours. The reaction mixture was concentrated in vacuo. The residue was coevaporated with EtOH (3×). The residue, redissolved in DMF (2 mL), was purified by prep. HPLC (column: Atlantis, 19×30 mm, 5 um, UV/MS, acidic conditions) and evaporated to give the desired amine as a yellow oil.

Workup

  1. customThe flask was carefully evacuated
  2. additionrefilled with H2 (3×)
  3. filtrationThe black suspension was filtered through Celite
  4. washThe Celite was rinsed with EtOH
  5. concentrationThe filtrate was concentrated in vacuo
  6. temperatureTo an ice-cooled solution of the residue in DCM (1.8 mL)
  7. addition4M HCl in dioxane (2.6 mL) was added
  8. stirringThe resulting solution was stirred at r.t. for 18 hours
  9. concentrationThe reaction mixture was concentrated in vacuo
  10. dissolutionThe residue, redissolved in DMF (2 mL)
  11. customwas purified by prep
  12. customHPLC (column: Atlantis, 19×30 mm, 5 um, UV/MS, acidic conditions) and evaporated

Sources & evidence

ORD record
ord-334f3697ebf449748e0e46aef136d398
Source dataset
uspto-grants-2013_11
Patent number
US08575158B2

Reaction notes

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