Acetic Acid → Dimethyl (3R)-5-bromo-3,4-dihydro-1H-isoquinoline-2,3-dicarboxylate

HRID 1854544Notes

Reaction equation

HRID 1854544 reaction equation
[Br:1][C:2]1[CH:18]=[CH:17][CH:16]=[CH:15][C:3]=1[CH2:4][C@H:5]([C:11]([O:13][CH3:14])=[O:12])[NH:6][C:7]([O:9][CH3:10])=[O:8].C=O.[C:21](O)(=O)C.S(=O)(=O)(O)O>>[Br:1][C:2]1[CH:18]=[CH:17][CH:16]=[C:15]2[C:3]=1[CH2:4][C@H:5]([C:11]([O:13][CH3:14])=[O:12])[N:6]([C:7]([O:9][CH3:10])=[O:8])[CH2:21]2

Participants

5

Reactant 4

HCID 176Acetic AcidHCID 712FormaldehydeHCID 1118Sulfuric AcidHCID 117720331Methyl 2-bromo-N-(methoxycarbonyl)-D-phenylalaninate

Product 1

HCID 117722930Dimethyl (3R)-5-bromo-3,4-dihydro-1H-isoquinoline-2,3-dicarboxylateYield 91.2%

Procedure

Stir a mixture of methyl 2-bromo-N-(methoxycarbonyl)-D-phenylalaninate (29.1 g, 92.10 mmol) and paraformaldehyde (9.13 g, 101.3 mmol) in glacial acetic acid (115 mL, 2.01 mol) and concentrated sulfuric acid (38.4 mL, 719.9 mmol) at room temperature for 7 hours. Partition between water and ethyl acetate. Separate the layers and extract the aqueous layer with ethyl acetate. Combine the ethyl acetate extracts and dry over sodium sulfate, filter, and concentrate under reduced pressure. Purify the residue by silica gel chromatography eluting with ethyl acetate: hexanes (5-40% gradient) to give the title compound (27.6 g, 84.0 mmol). MS (m/z): 328 (M+1).

Workup

  1. customPartition between water and ethyl acetate
  2. customSeparate the layers
  3. extractionextract the aqueous layer with ethyl acetate
  4. dry with materialdry over sodium sulfate
  5. filtrationfilter
  6. concentrationconcentrate under reduced pressure
  7. customPurify the residue by silica gel chromatography
  8. washeluting with ethyl acetate

Sources & evidence

ORD record
ord-a5a8b67700c040f194d8f1b09a91be89
Source dataset
uspto-grants-2015_02
Patent number
US08962654B2

Reaction notes

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