Sodium borohydride → tert-Butyl 8-bromo-4-hydroxy-3,4-dihydroisoquinoline-2(1H)-carboxylate

HRID 920241Notes

Reaction equation

HRID 920241 reaction equation
[Br:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:11]=1[CH2:10][N:9]([C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[CH2:8][C:7]2=[O:19].[BH4-].[Na+]>C1COCC1>[Br:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:11]=1[CH2:10][N:9]([C:12]([O:14][C:15]([CH3:17])([CH3:16])[CH3:18])=[O:13])[CH2:8][CH:7]2[OH:19]

Participants

4

Reactant 2

HCID 4311764Sodium borohydrideHCID 89525062tert-butyl 8-bromo-4-oxo-3,4-dihydroisoquinoline-2(1H)-carboxylate

Product 1

HCID 89526028tert-Butyl 8-bromo-4-hydroxy-3,4-dihydroisoquinoline-2(1H)-carboxylate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a flask containing tert-butyl 8-bromo-4-oxo-3,4-dihydroisoquinoline-2(1H)-carboxylate (24-3) (644 mg, 1.974 mmol) was added anhydrous THF (5 ml), followed by NaBH4 (399 mg, 10.55 mmol). The reaction mixture was then capped (not under N2) & stirred at room temperature. Followed by LC/MS. After 10 minutes the reaction mixture was quenched with saturated NaHCO3, then suspended in EtOAc, washed with saturated NaHCO3, then H2O, then brine; organics dried over Na2SO4, filtered & concentrated. Purification by silica gel chromatography (0-50% EtOAc/Hex; 40 g ISCO); desired fractions concentrated to yield tert-butyl 8-bromo-4-hydroxy-3,4-dihydroisoquinoline-2(1H)-carboxylate (24-4). HRMS [M+H]: calculated; 328.0543, observed; 328.0537.

Workup

  1. customThe reaction mixture was then capped (not under N2) &
  2. customAfter 10 minutes the reaction mixture was quenched with saturated NaHCO3
  3. washwashed with saturated NaHCO3
  4. dry with materialorganics dried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customPurification by silica gel chromatography (0-50% EtOAc/Hex; 40 g ISCO)
  8. concentrationdesired fractions concentrated

Sources & evidence

ORD record
ord-ff2473f9d7df430497b094d9ca391882
Source dataset
uspto-grants-2016_03
Patent number
US09273040B2

Reaction notes

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