Diisopropylethylamine → Tert-butyl 8-bromo-1,2,3,4-tetrahydroisoquinoline-2-carboxylate

HRID 1712945Notes

Reaction equation

HRID 1712945 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[CH2:8][NH:7][CH2:6][CH2:5]2.[Br:12][C:13]1[CH:14]=[CH:15][CH:16]=[C:17]2[C:22]=1[CH2:21][NH:20][CH2:19][CH2:18]2.CCN(C(C)C)C(C)C.[O:32]([C:40]([O:42][C:43]([CH3:46])([CH3:45])[CH3:44])=[O:41])[C:33]([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=O>C1COCC1>[Br:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[CH2:8][N:7]([C:33]([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:32])[CH2:6][CH2:5]2.[Br:12][C:13]1[CH:14]=[CH:15][CH:16]=[C:17]2[C:22]=1[CH2:21][N:20]([C:40]([O:42][C:43]([CH3:44])([CH3:45])[CH3:46])=[O:41])[CH2:19][CH2:18]2

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 90495Di-tert-butyl dicarbonateHCID 126304208-Bromo-1,2,3,4-tetrahydroisoquinolineHCID 158851836-Bromo-1,2,3,4-tetrahydroisoquinoline

Product 2

HCID 49761184tert-Butyl 6-bromo-3,4-dihydroisoquinoline-2(1H)-carboxylateHCID 59463272Tert-butyl 8-bromo-1,2,3,4-tetrahydroisoquinoline-2-carboxylateYield 88%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a mixture of 6-bromo-1,2,3,4-tetrahydroisoquinoline and 8-bromo-1,2,3,4-tetrahydroisoquinoline (22.1 mmol) in THF (100 mL) was added DIPEA (22.1 mmol) and BOC2O (24 mmol). The reaction mixture was allowed to stir at rt over the weekend and then concentrated. Water (5 mL) was added to the residue and the pH was adjusted to 2 by the addition of 1N H3PO4. The mixture was extracted with EtOAc. The organic solutions were combined, dried over Na2SO4, filtered and concentrated. The residue was purified by column chromatography to give tert-butyl 6-bromo-3,4-dihydroisoquinoline-2(1H)-carboxylate and tert-butyl 8-bromo-3,4-dihydroisoquinoline-2(1H)-carboxylate (6.04 g, 88%) as a yellow oil.

Workup

  1. concentrationconcentrated
  2. additionWater (5 mL) was added to the residue
  3. additionthe pH was adjusted to 2 by the addition of 1N H3PO4
  4. extractionThe mixture was extracted with EtOAc
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was purified by column chromatography

Sources & evidence

ORD record
ord-9d7c1c6c5dc740fa9de855b712b4577e
Source dataset
uspto-grants-2010_09
Patent number
US07795249B2

Reaction notes

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