Iodine → tert-butyl 3-(3-oxohept-6-enyl)-3,4-dihydroisoquinoline-2(1H)-carboxylate

HRID 579534Notes

Reaction equation

HRID 579534 reaction equation
[Mg].II.Br[CH2:5][CH2:6][CH:7]=[CH2:8].CON(C)[C:12](=[O:32])[CH2:13][CH2:14][CH:15]1[CH2:24][C:23]2[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=2)[CH2:17][N:16]1[C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26].[Cl-].[NH4+]>C1COCC1>[O:32]=[C:12]([CH2:8][CH2:7][CH:6]=[CH2:5])[CH2:13][CH2:14][CH:15]1[CH2:24][C:23]2[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=2)[CH2:17][N:16]1[C:25]([O:27][C:28]([CH3:30])([CH3:31])[CH3:29])=[O:26]

Participants

7

Reactant 5

HCID 807IodineHCID 21241Homoallyl bromideHCID 25517Ammonium ChlorideHCID 5462224Magnesium2×HCID 86663726tert-butyl 3-(3-(methoxy(methyl)amino)-3-oxopropyl)-3,4-dihydroisoquinoline-2(1H)-carboxylate

Product 1

HCID 66833329tert-butyl 3-(3-oxohept-6-enyl)-3,4-dihydroisoquinoline-2(1H)-carboxylateYield 95%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

While under an atmosphere of argon, a flame-dried round-bottomed flask was charged with magnesium (1.5 g, 62.9 mmol) a small crystal of I2 and just enough dry THF to cover the magnesium. The mixture was heated to reflux until the color dissipated (about 10 min). Approximately 10% of a solution of 4-bromo-1-butene (61.7 mmol) in THF (100 mL) was added all at once. The remainder of the solution was added dropwise while maintaining a gentle reflux. After the addition was complete, heating was continued for 5 min (until almost all of the Mg had reacted). The newly formed Grignard reagent was then added to an ice cooled solution of tert-butyl 3-(3-(methoxy(methyl)amino)-3-oxopropyl)-3,4-dihydroisoquinoline-2(1H)-carboxylate (8.6 g, 24.7 mmol) in dry THF (100 mL). After stirring overnight at room temperature, the solution was poured into saturated aqueous ammonium chloride and extracted with ether (3×). The combined organic extracts were dried over MgSO4, filtered and concentrated under reduced pressure to give tert-butyl 3-(3-oxohept-6-enyl)-3,4-dihydroisoquinoline-2(1H)-carboxylate (8.0 g, 95%). ESI MS found for C21H29NO3 m/z [366.5 (M+23)]. The crude product was used without further purification.

Workup

  1. temperatureThe mixture was heated
  2. temperatureto reflux until the color
  3. custom(about 10 min)
  4. additionThe remainder of the solution was added dropwise
  5. temperaturewhile maintaining a gentle reflux
  6. additionAfter the addition
  7. temperatureheating
  8. extractionextracted with ether (3×)
  9. dry with materialThe combined organic extracts were dried over MgSO4
  10. filtrationfiltered
  11. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-685fa23e9cba481ea347f4f36e2fb27c
Source dataset
uspto-grants-2015_05
Patent number
US09040703B2

Reaction notes

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