Formaldehyde → (R)-1,2,3,4-Tetrahydro-3-isoquinolinecarboxylic acid

HRID 1727216Notes

Reaction equation

HRID 1727216 reaction equation
[NH2:1][C@@H:2]([C:10]([OH:12])=[O:11])[CH2:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.[CH2:13]=O>>[CH2:13]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH2:3][C@H:2]([C:10]([OH:12])=[O:11])[NH:1]1

Participants

3

Reactant 2

HCID 712FormaldehydeHCID 71567D-Phenylalanine

Product 1

HCID 712398(R)-1,2,3,4-Tetrahydro-3-isoquinolinecarboxylic acidYield 42%

Procedure

D-Phenylalanine (50 g, 0.3 mol) concentrated hydrochloric acid (386 ml), and formalin (37% wt, 113.7 ml) were heated at 95° C. with vigorous stirring for 4 h. The reaction mixture was cooled to room temperature and stirred for a further 2 h. The reaction mixture was filtered and the precipitate washed with cold water to give (3R)-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid as a white solid (25 g, 42%). Benzyl alcohol (64 g) and p-toluene sulphonic acid (26.9 g) were added and the reaction mixture was refluxed in benzene (400 ml) under Dean Stark conditions. The solvent was removed in vacuo, the crude residue was triturated with diethyl ether to give a solid which was then recrystallised from water and methanol to give the title compound as a white solid (28 g, 35%).

Workup

  1. stirringstirred for a further 2 h
  2. filtrationThe reaction mixture was filtered
  3. washthe precipitate washed with cold water

Sources & evidence

ORD record
ord-dae4ee0d88504326a6bcd0761c25bcb8
Source dataset
uspto-grants-2009_02
Patent number
US07494992B2

Reaction notes

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