Water → 2-amino-5-(1,4-dioxaspiro[4.5]dec-7-en-8-yl)-N-methylbenzamide

HRID 511342

Reaction equation

HRID 511342 reaction equation
[NH2:1][C:2]1[CH:11]=[CH:10][C:9](Br)=[CH:8][C:3]=1[C:4]([NH:6][CH3:7])=[O:5].[O:13]1[C:17]2([CH2:22][CH2:21][C:20](B3OC(C)(C)C(C)(C)O3)=[CH:19][CH2:18]2)[O:16][CH2:15][CH2:14]1.ClCCl.O1CCOCC1.C(=O)([O-])[O-].[K+].[K+].O>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[NH2:1][C:2]1[CH:11]=[CH:10][C:9]([C:20]2[CH2:21][CH2:22][C:17]3([O:16][CH2:15][CH2:14][O:13]3)[CH2:18][CH:19]=2)=[CH:8][C:3]=1[C:4]([NH:6][CH3:7])=[O:5]

Participants

8

Reactant 6

HCID 962WaterHCID 6344DichloromethaneHCID 11430Potassium CarbonateHCID 312751,4-DioxaneHCID 36970768-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-1,4-dioxaspiro(4.5)dec-7-eneHCID 509995112-Amino-5-bromo-N-methylbenzamide2×

Product 1

HCID 672552222-amino-5-(1,4-dioxaspiro[4.5]dec-7-en-8-yl)-N-methylbenzamide

Reagents, catalysts & solvents 1

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)Catalyst

Procedure

2-Amino-5-bromo-N-methyl-benzamide (Compound 106A, 645.0 mg, 2.816 mmol), 1,4-dioxaspiro[4,5]dec-7-ene-8-boronic acid pinacol ester (899.2 mg, 3.379 mmol) and [1,1′-Bis(diphenylphosphino)ferrocene]dichloropalladium(II), complex with dichloromethane (1:1) (229.9 mg, 0.2816 mmol) were added to a 20 mL microwave tube and taken up in 1,4-Dioxane (8 mL, 100 mmol). This mixture was treated with a solution of potassium carbonate (1167 mg, 8.447 mmol) in H2O (3 mL, 200 mmol). After sparging the mixture with N2 for 1 minute, the tube was sealed and irradiated in the Biotage microwave reactor for 30 minutes at 100° C. The mixture was poured into water and extracted twice with EtOAc. The combined organic layers were washed with brine, dried over Na2SO4, filtered and concentrated to a black goo. This was taken up in DCM, treated with silica and concentrated to a plug. This plug was loaded into a sample cartridge and purified on an ISCO Combiflash unit (0-40%-70% EtOAc/Hexane) to isolate the desired product as 359 mg of a white solid. 1H NMR (400 MHz, DMSO-d6) δ 1.78 (t, J=6.44 Hz, 2H), 2.33 (br. s., 2H), 2.50-2.51 (m, J=1.80 Hz, 2H), 2.72 (d, J=4.55 Hz, 3H), 3.91 (s, 4H), 5.85 (t, J=3.92 Hz, 1H), 6.41 (s, 2H), 6.63 (d, J=8.59 Hz, 1H), 7.23 (dd, J=8.59, 2.02 Hz, 1H), 7.48 (d, J=2.27 Hz, 1H), 8.23 (d, J=4.29 Hz, 1H). MS (ES+): m/z=289.06 (100) [M+1]. HPLC: tR=2.62 min (ZQ3, polar—5 min).

Workup

  1. customAfter sparging the mixture with N2 for 1 minute
  2. customthe tube was sealed
  3. customirradiated in the Biotage microwave reactor for 30 minutes at 100° C
  4. additionThe mixture was poured into water
  5. extractionextracted twice with EtOAc
  6. washThe combined organic layers were washed with brine
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated to a black goo
  10. additiontreated with silica
  11. concentrationconcentrated to a plug
  12. custompurified on an ISCO Combiflash unit (0-40%-70% EtOAc/Hexane)

Sources & evidence

ORD record
ord-117fa4e146d44fbd85c919261b55c6f0
Source dataset
uspto-grants-2015_08
Patent number
US09096624B2

Linked notes

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