Ethyl bromoacetate → HCID 66655039, compound

HRID 2036219Notes

Reaction equation

HRID 2036219 reaction equation
C(OC([N:11]1[CH2:20][CH2:19][C:18]2[C:13](=[CH:14][CH:15]=[C:16]([F:22])[C:17]=2Br)[CH:12]1[C:23]1[CH:28]=[C:27]([F:29])[CH:26]=[CH:25][C:24]=1[OH:30])=O)C1C=CC=CC=1.C([O-])([O-])=O.[Cs+].[Cs+].Br[CH2:38][C:39]([O:41][CH2:42][CH3:43])=[O:40]>CN(C=O)C>[CH2:42]([O:41][C:39](=[O:40])[CH2:38][O:30][C:24]1[CH:25]=[CH:26][C:27]([F:29])=[CH:28][C:23]=1[CH:12]1[C:13]2[C:18](=[CH:17][C:16]([F:22])=[CH:15][CH:14]=2)[CH2:19][CH2:20][NH:11]1)[CH3:43]

Participants

5

Reactant 3

HCID 7748Ethyl bromoacetateHCID 10796Cesium carbonateHCID 66653905HCID 66653905, compound

Product 1

HCID 66655039HCID 66655039, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of (±)-5-bromo-6-fluoro-1-(5-fluoro-2-hydroxy-phenyl)-3,4-dihydro-1H-isoquinoline-2-carboxylic acid benzyl ester (50 mg, 0.11 mmol, 1.0 eq.) and Cs2CO3 (104 mg, 0.32 mmol, 3.0 eq.) in DMF (1 mL), ethyl bromoacetate (18 μL, 0.16 mmol, 1.5 eq.) was added. The resulting solution was stirred at r.t. for 18 hours. The solvent was evaporated and the mixture was poured into water and extracted with DCM (3×). The combined extracts were washed with water and dried over MgSO4. To a solution under N2 of the residue in EtOH (4 mL), palladium on activated carbon (10 wt. %, 10 mg) was added. The flask was evacuated and backfilled with H2 (3×). The black suspension was stirred at r.t. under an H2-atmosphere for 18 hours. The suspension was filtered through Celite, the Celite rinsed with EtOH, and the filtrate was concentrated in vacuo. The residue was purified by prep. HPLC (column: Waters X-bridge, 19×50 mm, 10 um, UV/MS, basic conditions) to give the title amine.

Workup

  1. customThe solvent was evaporated
  2. additionthe mixture was poured into water
  3. extractionextracted with DCM (3×)
  4. washThe combined extracts were washed with water
  5. dry with materialdried over MgSO4
  6. additionTo a solution under N2 of the residue in EtOH (4 mL), palladium on activated carbon (10 wt. %, 10 mg) was added
  7. customThe flask was evacuated
  8. stirringThe black suspension was stirred at r.t. under an H2-atmosphere for 18 hours
  9. filtrationThe suspension was filtered through Celite
  10. washthe Celite rinsed with EtOH
  11. concentrationthe filtrate was concentrated in vacuo
  12. customThe residue was purified by prep

Sources & evidence

ORD record
ord-b4ee7a0f5fa04f009fa7033ac1710aaa
Source dataset
uspto-grants-2013_11
Patent number
US08575158B2

Reaction notes

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