Hydrochloric Acid → (R)-5-Bromo-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid hydrochloride

HRID 1854545Notes

Reaction equation

HRID 1854545 reaction equation
[Br:1][C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[CH2:4][C@H:5]([C:16]([O:18]C)=[O:17])[N:6](C(OC)=O)[CH2:7]2.[ClH:20]>>[ClH:20].[Br:1][C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[CH2:4][C@H:5]([C:16]([OH:18])=[O:17])[NH:6][CH2:7]2

Participants

3

Reactant 2

HCID 313Hydrochloric AcidHCID 117722930Dimethyl (3R)-5-bromo-3,4-dihydro-1H-isoquinoline-2,3-dicarboxylate

Product 1

HCID 117720332(R)-5-Bromo-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid hydrochlorideYield 84.6%

Procedure

Dissolve dimethyl (3R)-5-bromo-3,4-dihydro-1H-isoquinoline-2,3-dicarboxylate (27.55 g, 84.0 mmol) in 5N hydrochloric acid (330.6 mL, 1.65 mol) and heat to reflux for three days. Concentrate under reduced pressure to give a white solid. Wash the solid with diethyl ether and dry under vacuum at 40° C. overnight to give (3R)-5-bromo-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid hydrochloride (1:1) (20.8 g, 71.1 mmol). Add acetyl chloride (50.6 mL, 711.0 mmol) to a 0° C. mixture of (3R)-5-bromo-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid hydrochloride (1:1) (20.8 g, 71.1 mmol) in methanol (474 mL). Warm to room temperature and stir for 36 hours. Concentrate under reduced pressure and dry to give the title compound (21.9 g, 71.4 mmol). MS (m/z): 270 (M+1).

Workup

  1. temperatureheat
  2. temperatureto reflux for three days
  3. concentrationConcentrate under reduced pressure
  4. customto give a white solid
  5. washWash the solid with diethyl ether
  6. customdry under vacuum at 40° C. overnight

Sources & evidence

ORD record
ord-bd71410e14b94592bfb4d2e3a186cd29
Source dataset
uspto-grants-2015_02
Patent number
US08962654B2

Reaction notes

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