Acetic Acid → 2-Benzyl-8-fluoro-1-(4-(trifluoromethyl)phenyl)-1,2,3,4-tetrahydroisoquinoline

HRID 445250Notes

Reaction equation

HRID 445250 reaction equation
[CH2:1]([N:8]1[CH:17]=[CH:16][C:15]2[C:10](=[C:11]([F:18])[CH:12]=[CH:13][CH:14]=2)[CH:9]1[C:19]1[CH:24]=[CH:23][C:22]([C:25]([F:28])([F:27])[F:26])=[CH:21][CH:20]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[BH4-].[Na+].C(O)(=O)C>O1CCCC1>[CH2:1]([N:8]1[CH2:17][CH2:16][C:15]2[C:10](=[C:11]([F:18])[CH:12]=[CH:13][CH:14]=2)[CH:9]1[C:19]1[CH:20]=[CH:21][C:22]([C:25]([F:28])([F:26])[F:27])=[CH:23][CH:24]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 176Acetic AcidHCID 4311764Sodium borohydrideHCID 573263062-Benzyl-8-fluoro-1-(4-(trifluoromethyl)phenyl)-1,2-dihydroisoquinoline

Product 1

HCID 573263072-Benzyl-8-fluoro-1-(4-(trifluoromethyl)phenyl)-1,2,3,4-tetrahydroisoquinoline

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A 250-mL round-bottomed flask containing a solution of 2-benzyl-8-fluoro-1-(4-(trifluoromethyl)phenyl)-1,2-dihydroisoquinoline (1.0 g, 2.6 mmol) in anhydrous tetrahydrofuran (20 mL) was treated with sodium borohydride (0.3 g, 8.4 mmol) at RT. After 20 min, acetic acid (3.3 mL) was added and the reaction was stirred at RT for 2.5 h. The reaction mixture was concentrated and the resulting residue was taken up in ethyl acetate (150 mL), water (25 mL), 1N sodium hydroxide, and brine (35 mL). The ethyl acetate layer was separated, dried over anhydrous sodium sulfate, and concentrated to yield the crude product. The crude product was purified by silica gel chromatography (20-30% EtOAc in hexanes) to give 2-benzyl-8-fluoro-1-(4-(trifluoromethyl)phenyl)-1,2,3,4-tetrahydroisoquinoline as a colorless oil. MS (ESI, pos. ion) m/z: 386 (M+1).

Workup

  1. concentrationThe reaction mixture was concentrated
  2. customThe ethyl acetate layer was separated
  3. dry with materialdried over anhydrous sodium sulfate
  4. concentrationconcentrated
  5. customto yield the crude product
  6. customThe crude product was purified by silica gel chromatography (20-30% EtOAc in hexanes)

Sources & evidence

ORD record
ord-143c59cca71a431fa6b4f99f35518116
Source dataset
uspto-grants-2013_07
Patent number
US08476297B2

Reaction notes

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