1,2-Dichloroethane → (S)-tert-Butyl 3-formyl-3,4-dihydroisoquinoline-2(1H)-carboxylate

HRID 1242744Notes

Reaction equation

HRID 1242744 reaction equation
[N:1]1([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:10][C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH2:3][C@H:2]1[C:11](O)=[O:12].Cl.CNOC.C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1.[H-].[H-].[H-].[H-].[Li+].[Al+3]>CCOCC.C(Cl)Cl>[C:14]([N:1]1[C@H:2]([CH:11]=[O:12])[CH2:3][C:4]2[C:9](=[CH:8][CH:7]=[CH:6][CH:5]=2)[CH2:10]1)([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15]

Participants

8

Reactant 5

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 81138Methanamine, N-methoxy-, hydrochloride (1:1)HCID 664088(3S)-2-((tert-butoxy)carbonyl)-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acidHCID 21226445Aluminium lithium hydride

Product 1

HCID 22861260(S)-tert-Butyl 3-formyl-3,4-dihydroisoquinoline-2(1H)-carboxylateYield 62.5%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

To a round-bottomed flask equipped with stirring was added Boc-L-Tic-OH (Bachem) (1 g, 3.6 mmol) and CH2Cl2 (20 mL), followed by TEA (0.5 mL, 3.6 mmol) and N,O-dimethylhydroxylamine hydrochloride. The reaction mixture was cooled to 0° C., EDC (690 mg, 3.6 mmol) and HOBT (550 mg, 3.6 mmol) were added, and the reaction mixture was stirred at 0° C. for 1 h then at RT for 18 h. The organic layer was washed with 0.5N HCl, satd NaHCO3, and brine. The organic layer was dried over Na2SO4, filtered and concentrated in vacuo to afford a colorless oil. Into a round bottomed flask equipped with magnetic stirring, was added the oil dissolved in Et2O (15 mL), and the flask was cooled to −78° C. LiAlH4 (1M in Et2O, Aldrich) (3.2 mL, 3.2 mmol) was added, and after 30 min the reaction was warmed to RT. The organic layer was washed with 0.5N HCl, satd NaHCO3, and brine. After drying the organic layer over Na2SO4, it was filtered and concentrated in vacuo to afford (3S)-N-Boc-1,2,3,4-tetrahydroisoquinoline-3-carbaldehyde as a colorless oil (588 mg).

Workup

  1. customTo a round-bottomed flask equipped
  2. stirringthe reaction mixture was stirred at 0° C. for 1 h
  3. washThe organic layer was washed with 0.5N HCl
  4. dry with materialThe organic layer was dried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customto afford a colorless oil
  8. customInto a round bottomed flask equipped with magnetic stirring
  9. additionwas added the oil
  10. temperaturethe flask was cooled to −78° C
  11. temperatureafter 30 min the reaction was warmed to RT
  12. washThe organic layer was washed with 0.5N HCl
  13. dry with materialAfter drying the organic layer over Na2SO4, it
  14. filtrationwas filtered
  15. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-93bb9121255c4de5a1f57db79230de14
Source dataset
uspto-grants-2006_10
Patent number
US07115607B2

Reaction notes

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