Diisobutylaluminum hydride → tert-Butyl 4-fluoro-8-(hydroxymethyl)-3,4-dihydroisoquinoline-2(1H)-carboxylate

HRID 920244Notes

Reaction equation

HRID 920244 reaction equation
[F:1][CH:2]1[C:11]2[C:6](=[C:7]([C:12](OC)=[O:13])[CH:8]=[CH:9][CH:10]=2)[CH2:5][N:4]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:3]1.C(=O)=O.CC(C)=O.CC(C[AlH]CC(C)C)C>C1COCC1>[F:1][CH:2]1[C:11]2[C:6](=[C:7]([CH2:12][OH:13])[CH:8]=[CH:9][CH:10]=2)[CH2:5][N:4]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:3]1

Participants

5

Reactant 3

HCID 14487Diisobutylaluminum hydrideHCID 18522661Acetone cardiceHCID 895258942-tert-Butyl 8-methyl 4-fluoro-3,4-dihydroisoquinoline-2,8(1H)-dicarboxylate

Product 1

HCID 89526277tert-Butyl 4-fluoro-8-(hydroxymethyl)-3,4-dihydroisoquinoline-2(1H)-carboxylate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a flask containing 2-tert-butyl 8-methyl 4-fluoro-3,4-dihydroisoquinoline-2,8(1H)-dicarboxylate (24-6) (214 mg, 0.692 mmol), was added anhydrous THF (3.5 ml) then cooled to −78 C (dry ice/acetone bath) while stirring under an atmosphere of N2. Then added DIBAL-H (2.4 ml, 2.400 mmol) dropwise. The reaction mixture was then stirred at −78 C for ˜20 minutes, then warmed to room temperature. Followed by LC/MS. After 10 minutes at room temperature quenched by dropwise addition of saturated solution of Rochelle's Salt (Na+/K+ Tartrate) in water, then suspended in EtOAc, washed with saturated NaHCO3, then H2O, then brine; organics dried over Na2SO4, filtered & concentrated. Purification by silica gel chromatography (0-40%; isocratic @ 30% EtOAc/Hex; 24 g ISCO); desired fractions concentrated to yield tert-butyl 4-fluoro-8-(hydroxymethyl)-3,4-dihydroisoquinoline-2(1H)-carboxylate (24-7). HRMS [M+H]; calculated; 282.1500, observed; 282.1491.

Workup

  1. stirringThe reaction mixture was then stirred at −78 C for ˜20 minutes
  2. customAfter 10 minutes at room temperature quenched by dropwise addition of saturated solution of Rochelle's Salt (Na+/K+ Tartrate) in water
  3. washwashed with saturated NaHCO3
  4. dry with materialorganics dried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customPurification by silica gel chromatography (0-40%; isocratic @ 30% EtOAc/Hex; 24 g ISCO)
  8. concentrationdesired fractions concentrated

Sources & evidence

ORD record
ord-1d1aca2cf53e49e9b71c49f2bbcb9d72
Source dataset
uspto-grants-2016_03
Patent number
US09273040B2

Reaction notes

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