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

HRID 228092Notes

Reaction equation

HRID 228092 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 0.5 N 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 0.5 N 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 0.5 N 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 0.5 N HCl
  13. dry with materialAfter drying the organic layer over Na2SO4, it
  14. filtrationwas filtered
  15. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-2e145f4613764b27b8eb5bc83a0d1a19
Source dataset
uspto-grants-2009_07
Patent number
US07560460B2

Reaction notes

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