Sodium Bicarbonate → 2-((1S,3R)-3-(((tert-butyldimethylsilyl)oxy)methyl)-2-(2-(2-chloro-6-fluorophenyl)acetyl)-1-methyl-1,2,3,4-tetrahydroisoquinolin-5-yl)acetaldehyde

HRID 1854575Notes

Reaction equation

HRID 1854575 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[CH2:20][CH2:21][OH:22])[C@H:12]([CH3:23])[N:11]1[C:24](=[O:34])[CH2:25][C:26]1[C:31]([F:32])=[CH:30][CH:29]=[CH:28][C:27]=1[Cl:33])([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].C([O-])(O)=O.[Na+]>C(Cl)Cl>[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][CH:21]=[O:22])[C@H:12]([CH3:23])[N:11]1[C:24](=[O:34])[CH2:25][C:26]1[C:31]([F:32])=[CH:30][CH:29]=[CH:28][C:27]=1[Cl:33])([C:4]([CH3:7])([CH3:5])[CH3:6])([CH3:3])[CH3:2]

Participants

4

Reactant 2

HCID 516892Sodium BicarbonateHCID 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

Product 1

HCID 1238567142-((1S,3R)-3-(((tert-butyldimethylsilyl)oxy)methyl)-2-(2-(2-chloro-6-fluorophenyl)acetyl)-1-methyl-1,2,3,4-tetrahydroisoquinolin-5-yl)acetaldehydeYield 81.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Dissolve 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 (1.08 g, 2.13 mmol) in CH2Cl2 (21 mL). Add NaHCO3 (1.08 g, 12.9 mmol) and 3,3,3-triacetoxy-3-iodophthalide (1.09 g, 2.56 mmol) at room temperature. Stir 40 min. Add saturated NaHCO3 solution and saturated Na2S2O3 solution, extract with ethyl acetate three times. Combine the ethyl acetate extracts, 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 the title compound as a white foam (0.87 g, 1.73 mmol).

Workup

  1. customat room temperature
  2. extractionAdd saturated NaHCO3 solution and saturated Na2S2O3 solution, extract with ethyl acetate three times
  3. dry with materialdry over sodium sulfate
  4. filtrationfilter
  5. concentrationconcentrate under reduced pressure
  6. customto give a residue
  7. customPurify the residue by silica gel chromatography
  8. washeluting with ethyl acetate

Sources & evidence

ORD record
ord-5f4b7dff582240898fe3885eb0d7f10d
Source dataset
uspto-grants-2015_02
Patent number
US08962654B2

Reaction notes

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