Formaldehyde → 1,2,3,4-Tetrahydroisoquinoline

HRID 1441478Notes

Reaction equation

HRID 1441478 reaction equation
Br[C:2]1[CH:3]=[C:4]([CH2:8][CH2:9][NH:10][C:11](=O)C(F)(F)F)[CH:5]=[CH:6][CH:7]=1.C=O.S(=O)(=O)(O)O>C(O)(=O)C>[CH2:11]1[C:3]2[C:4](=[CH:5][CH:6]=[CH:7][CH:2]=2)[CH2:8][CH2:9][NH:10]1

Participants

5

Reactant 3

HCID 712FormaldehydeHCID 1118Sulfuric AcidHCID 18414326N-[2-(3-Bromophenyl)ethyl]-2,2,2-trifluoroacetamide

Product 1

HCID 70461,2,3,4-Tetrahydroisoquinoline

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

Preferably the 1,2,3,4-tetrahydroisoquinoline intermediate (VIIa) is synthesised by Route A shown in Scheme 2. This route is a Friedel-Craft-type reaction of N-[2-(3-bromophenyl)ethyl]-2,2,2-trifluoroacetamide with formaldehyde and sulfuric acid in acetic acid (Tetrahedron Lett. 1996, 37(31), 5453-5456) giving a mixture of the 6-bromo- and 8-bromoisomer in a ratio of 3 to 1. Replacement of the trifluoroacetamide group with a BOC-group gives (VIIa). The regioisomers are not conveniently separated at this stage.

Workup

  1. customgiving

Sources & evidence

ORD record
ord-07b6af18c9f1435fa05e7913406b9a8e
Source dataset
uspto-grants-2010_02
Patent number
US07655664B2

Reaction notes

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