Hydrogen Peroxide → 1-((1S,3R)-3-(((tert-butyldimethylsilyl)oxy)methyl)-5-(2-hydroxyethyl)-1-methyl-3,4-dihydroisoquinolin-2(1H)-yl)-2-(2-chloro-6-fluorophenyl)ethan-1-one

HRID 1854574Notes

Reaction equation

HRID 1854574 reaction equation
[Si:1]([O:8][CH2:9][C@H:10]1[CH2:19][C:18]2[C:13](=[CH:14][CH:15]=[CH:16][C:17]=2[CH:20]=[CH2:21])[C@H:12]([CH3:22])[N:11]1[C:23](=[O:33])[CH2:24][C:25]1[C:30]([F:31])=[CH:29][CH:28]=[CH:27][C:26]=1[Cl:32])([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[OH-:34].[Na+].OO>C1COCC1>[Si:1]([O:8][CH2:9][C@H:10]1[CH2:19][C:18]2[C:13](=[CH:14][CH:15]=[CH:16][C:17]=2[CH2:20][CH2:21][OH:34])[C@H:12]([CH3:22])[N:11]1[C:23](=[O:33])[CH2:24][C:25]1[C:30]([F:31])=[CH:29][CH:28]=[CH:27][C:26]=1[Cl:32])([C:4]([CH3:5])([CH3:6])[CH3:7])([CH3:3])[CH3:2]

Participants

5

Reactant 3

HCID 784Hydrogen PeroxideHCID 14798Sodium HydroxideHCID 1235332471-((1S,3R)-3-(((tert-butyldimethylsilyl)oxy)methyl)-1-methyl-5-vinyl-3,4-dihydroisoquinolin-2(1H)-yl)-2-(2-chloro-6-fluorophenyl)ethan-1-one

Product 1

HCID 1239773771-((1S,3R)-3-(((tert-butyldimethylsilyl)oxy)methyl)-5-(2-hydroxyethyl)-1-methyl-3,4-dihydroisoquinolin-2(1H)-yl)-2-(2-chloro-6-fluorophenyl)ethan-1-one

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

Dissolve 1-((1S,3R)-3-(((tert-butyldimethylsilyl)oxy)methyl)-1-methyl-5-vinyl-3,4-dihydroisoquinolin-2(1H)-yl)-2-(2-chloro-6-fluorophenyl)ethan-1-one (1.54 g, 3.15 mmol) in THF (31 mL). Cool to 0° C. Add BH3 (6.3 mL, 6.3 mmol, 1M in THF). Stir 4 h at room temperature. Cool to 0° C. Add NaOH (12.6 mL, 3 M in water) and H2O2 (1.92 mL, 30% wt/wt % in water). Stir overnight at room temperature. Add ethyl acetate, wash with saturated NaHCO3 solution and brine, dry over sodium sulfate, filter, and concentrate under reduced pressure to give a residue. Purify the residue by silica gel chromatography, eluting with ethyl acetate: hexanes (gradient, 5-60%) to give 1-((1S,3R)-3-(((tert-butyldimethylsilyl)oxy)methyl)-5-(2-hydroxyethyl)-1-methyl-3,4-dihydroisoquinolin-2(1H)-yl)-2-(2-chloro-6-fluorophenyl)ethan-1-one as a white foam (1.08 g, 2.13 mmol). MS (m/z): 506.2 (M+1).

Workup

  1. additionAdd
  2. temperatureCool to 0° C
  3. stirringStir overnight at room temperature
  4. washAdd ethyl acetate, wash with saturated NaHCO3 solution and brine
  5. dry with materialdry over sodium sulfate
  6. filtrationfilter
  7. concentrationconcentrate under reduced pressure
  8. customto give a residue
  9. customPurify the residue by silica gel chromatography
  10. washeluting with ethyl acetate

Sources & evidence

ORD record
ord-4426d8915149450782d1613b6047351a
Source dataset
uspto-grants-2015_02
Patent number
US08962654B2

Reaction notes

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