Dimethylformamide → tert-Butyl 4-formyl-3-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)benzoate

HRID 528963

Reaction equation

HRID 528963 reaction equation
[C]=O.I[C:4]1[CH:16]=[CH:15][C:7]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])=[CH:6][C:5]=1[C:17]([N:19]1[CH2:28][CH2:27][C:26]2[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=2)[CH2:20]1)=[O:18].CCN(C(C)C)C(C)C.C([SiH](CCCCCCCC)CCCCCCCC)CCCCCCC.CN([CH:66]=[O:67])C>CCOC(C)=O.C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2].[Pd](Cl)Cl>[CH:66]([C:4]1[CH:16]=[CH:15][C:7]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])=[CH:6][C:5]=1[C:17]([N:19]1[CH2:28][CH2:27][C:26]2[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=2)[CH2:20]1)=[O:18])=[O:67]

Participants

9

Reactant 5

HCID 6228DimethylformamideHCID 81531DiisopropylethylamineHCID 87780Trioctylsilane, 95%HCID 71062274tert-Butyl 4-iodo-3-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)benzoateHCID 178418416HCID 178418416, compound

Product 1

HCID 86718914tert-Butyl 4-formyl-3-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)benzoateYield 50%

Reagents, catalysts & solvents 3

HCID 24290Palladium ChlorideCatalystHCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)CatalystHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
70 °C

Procedure

Carbon monoxide was bubbled through a solution of tert-butyl 4-iodo-3-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)benzoate (1.36 g, 2.94 mmol) and 1,1′-bis-(diphenylphosphino)-ferrocene) palladium dichloride (0.241 g, 0.294 mmol) in DMF (20 mL) at 70° C. for 10 min. DIPEA (1.28 mL, 7.34 mmol) and trioctylsilane (2.64 mL, 5.87 mmol) were added. The reaction mixture was stirred at 70° C. under CO (balloon) overnight. After cooling to room temperature, the reaction mixture was diluted with EtOAc and washed with sat. aq. sodium bicarbonate solution, 10% aq. LiCl solution, and then sat. aq. sodium bicarbonate solution again. The organic layer was dried over anhydrous sodium sulfate and concentrated in vacuo. The residue was purified by flash chromatography (Isco 40 g column eluting from 0-40% EtOAc/hexanes) to give the title compound (537 mg, 50%) as a yellow foam. 1H NMR (CDCl3, 1.5:1 mixture of amide rotamers) δ 10.19 (s, 0.5H), 10.14 (s, 0.5H), 8.17-8.13 (m, 1H), 8.03-7.98 (m, 2H), 7.26-7.10 (m, 4H), 5.00 (s, 1H), 4.33 (m, 1H), 4.09 (t, J=6 Hz, 1H), 3.45 (t, J=6 Hz, 1H), 3.04 (t, J=6 Hz, 1H), 2.80 (t, J=6 Hz, 1H), 1.61 (s, 9H); MS(ESI+) m/z 366.2 (M+H)+.

Workup

  1. temperatureAfter cooling to room temperature
  2. washwashed with sat. aq. sodium bicarbonate solution, 10% aq. LiCl solution
  3. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  4. concentrationconcentrated in vacuo
  5. customThe residue was purified by flash chromatography (Isco 40 g column eluting from 0-40% EtOAc/hexanes)

Sources & evidence

ORD record
ord-b52b009c081e42fcbdc7882989b6f5a3
Source dataset
uspto-grants-2016_05
Patent number
US09346795B2

Linked notes

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