Ethanol → HCID 82579807, compound

HRID 629812Notes

Reaction equation

HRID 629812 reaction equation
[Br:1][C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[CH2:4][CH2:5][N:6](C(OCC)=O)[CH:7]2[C:12]([OH:14])=[O:13].[CH3:20]CO.[OH-].[Na+].S(Cl)(Cl)=O>O1CCOCC1>[Br:1][C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[CH2:4][CH2:5][NH:6][CH:7]2[C:12]([O:14][CH3:20])=[O:13]

Participants

6

Reactant 4

HCID 702EthanolHCID 14798Sodium HydroxideHCID 24386Thionyl ChlorideHCID 15171945HCID 15171945, compound

Product 1

HCID 82579807HCID 82579807, compoundYield 80%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

5-Bromo-2-(ethoxycarbonyl)-1,2,3,4-tetrahydroisoquinoline-1-carboxylic acid (1 g, 3.05 mmol) (Ortwine, et al., J. Med. Chem, 1992, 35, 1345), in two batches, was heated in a microwave to 150° C. in 1,4-dioxane (4 mL)/EtOH (2 mL)/2N NaOH (5 mL) for a total of 3 h. The combined reaction mixtures were concentrated, dissolved in MeOH (30 mL) and thionyl chloride (0.222 mL, 3.05 mmol) was slowly added. After 18 h, the solvent was removed and the residue was partitioned with EtOAc (50 mL)/saturated NaHCO3 (30 mL), phases separated and aqueous layer was extracted with EtOAc (2×25 mL). The combined organic layers were washed with brine (25 mL) and dried (MgSO4) to afford 0.56 g (80%) of Intermediate 4A as a yellow oil. MS (ESI) m/z: 270-272 (M+H)+.

Workup

  1. customThe combined reaction mixtures
  2. concentrationwere concentrated
  3. dissolutiondissolved in MeOH (30 mL)
  4. customthe solvent was removed
  5. customthe residue was partitioned with EtOAc (50 mL)/saturated NaHCO3 (30 mL), phases
  6. customseparated
  7. extractionaqueous layer was extracted with EtOAc (2×25 mL)
  8. washThe combined organic layers were washed with brine (25 mL)
  9. dry with materialdried (MgSO4)

Sources & evidence

ORD record
ord-95a405542a79476486c51971eadbe4f2
Source dataset
uspto-grants-2016_04
Patent number
US09315519B2

Reaction notes

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