Triacetoxyperiodinane → tert-butyl 7-chloro-3-formyl-3,4-dihydroisoquinoline-2(1H)-carboxylate

HRID 61397Notes

Reaction equation

HRID 61397 reaction equation
[Cl:1][C:2]1[CH:11]=[C:10]2[C:5]([CH2:6][CH:7]([CH2:19][OH:20])[N:8]([C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[CH2:9]2)=[CH:4][CH:3]=1.CC(OI1(OC(C)=O)(OC(C)=O)OC(=O)C2C=CC=CC1=2)=O>C(Cl)Cl>[Cl:1][C:2]1[CH:11]=[C:10]2[C:5]([CH2:6][CH:7]([CH:19]=[O:20])[N:8]([C:12]([O:14][C:15]([CH3:16])([CH3:17])[CH3:18])=[O:13])[CH2:9]2)=[CH:4][CH:3]=1

Participants

4

Reactant 2

HCID 159087TriacetoxyperiodinaneHCID 67517810HCID 67517810, compound

Product 1

HCID 86665792tert-butyl 7-chloro-3-formyl-3,4-dihydroisoquinoline-2(1H)-carboxylateYield 60.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

While under nitrogen, a stirred solution of tert-butyl 7-chloro-3-(hydroxymethyl)-3,4-dihydroisoquinoline-2(1H)-carboxylate (Step 6, 270 mg, 0.907 mmol) in methylene chloride (11 mL) was cooled in an ice-water batch and treated dropwise with a solution of Dess-Martin periodinane (461 mg, 1.09 mmol) in methylene chloride (3 mL) over several minutes. The cooling bath was removed, and the resulting clear mixture was stirred at room temperature for 1.5 h. Once complete, the mixture was re-cooled in an ice-water bath, quenched portionwise with a 1:1 mixture of saturated aqueous Na2S2O3 and saturated aqueous NaHCO3 (20 mL total) and stirred for 10 min at room temperature. The layers were separated, the aqueous phase was re-extracted with methylene chloride (20 mL), and the combined organic phase was washed with saturated aqueous sodium chloride (10 mL), dried over Na2SO4 and concentrated under reduced pressure. Purification by silica gel chromatography (40 g column, 10-30% ethyl acetate in hexanes) gave tert-butyl 7-chloro-3-formyl-3,4-dihydroisoquinoline-2(1H)-carboxylate (162 mg, 60%) as a clear gum. 1H NMR (DMSO-d6, 400 MHz) δ 9.45 (bs, 1 H), 7.34 (m, 1 H), 7.26 (m, 2 H), 4.78 (m, ˜0.5 H), 4.64 (m, ˜0.5 H), 4.50 (m, 2 H), 3.21 (m, 1 H), 3.05 (m, 1 H), 1.46 (s, ˜4.5 H), 1.38 (s, ˜4.5 H) mixture of rotamers).

Workup

  1. customThe cooling bath was removed
  2. temperatureOnce complete, the mixture was re-cooled in an ice-water bath
  3. customquenched portionwise with a 1:1 mixture of saturated aqueous Na2S2O3 and saturated aqueous NaHCO3 (20 mL total)
  4. stirringstirred for 10 min at room temperature
  5. customThe layers were separated
  6. extractionthe aqueous phase was re-extracted with methylene chloride (20 mL)
  7. washthe combined organic phase was washed with saturated aqueous sodium chloride (10 mL)
  8. dry with materialdried over Na2SO4
  9. concentrationconcentrated under reduced pressure
  10. customPurification by silica gel chromatography (40 g column, 10-30% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-2468f426850a4c71b05eb294a3bab8d1
Source dataset
uspto-grants-2016_09
Patent number
US09440995B2

Reaction notes

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