Water → ethyl 4-(2-methyl-7-nitro-1-oxo-2,3-dihydro-1H-isoindol-4-yl)cyclohex-3-ene-1-carboxylate

HRID 511241Notes

Reaction equation

HRID 511241 reaction equation
[CH3:1][N:2]1[CH2:10][C:9]2[C:4](=[C:5]([N+:20]([O-:22])=[O:21])[CH:6]=[CH:7][C:8]=2B2OC(C)(C)C(C)(C)O2)[C:3]1=[O:23].FC(F)(F)S(O[C:30]1[CH2:35][CH2:34][CH:33]([C:36]([O:38][CH2:39][CH3:40])=[O:37])[CH2:32][CH:31]=1)(=O)=O.C(=O)([O-])[O-].[K+].[K+].ClCCl.O1CCOCC1.O>C1C=CC(P([C]2[CH][CH][CH][CH]2)C2C=CC=CC=2)=CC=1.C1C=CC(P([C]2[CH][CH][CH][CH]2)C2C=CC=CC=2)=CC=1.Cl[Pd]Cl.[Fe]>[CH3:1][N:2]1[CH2:10][C:9]2[C:4](=[C:5]([N+:20]([O-:22])=[O:21])[CH:6]=[CH:7][C:8]=2[C:30]2[CH2:35][CH2:34][CH:33]([C:36]([O:38][CH2:39][CH3:40])=[O:37])[CH2:32][CH:31]=2)[C:3]1=[O:23]

Participants

8

Reactant 6

HCID 962WaterHCID 6344DichloromethaneHCID 11430Potassium CarbonateHCID 312751,4-DioxaneHCID 9861195Ethyl 4-(((trifluoromethyl)sulfonyl)oxy)cyclohex-3-enecarboxylateHCID 672539682-Methyl-7-nitro-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-2,3-dihydro-isoindol-1-one

Product 1

HCID 67253669ethyl 4-(2-methyl-7-nitro-1-oxo-2,3-dihydro-1H-isoindol-4-yl)cyclohex-3-ene-1-carboxylateYield 63.4%

Reagents, catalysts & solvents 1

HCID 178477754HCID 178477754, compoundCatalyst

Procedure

A mixture of 2-methyl-7-nitro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2,3-dihydro-1H-isoindol-1-one (1.50 g, 4.72 mmol), ethyl 4-{[(trifluoromethyl)sulfonyl]oxy}cyclohex-3-ene-1-carboxylate (1.57 g, 5.19 mmol), potassium carbonate (1.95 g, 14.1 mmol) and [1,1-bis(diphenylphosphino)ferrocene]dichloropalladium(II), complex with dichloromethane (1:1) (0.385 g, 0.472 mmol) in 1,4-dioxane (12.0 mL, 154 mmol) and H2O (3.00 mL, 166 mmol) was evacuated and refilled with Ar(g)((3×) and irradiated in the microwave at 100° C. for 30 min. The crude mixture was concentrated in vacuo to a solid and purified by CombiFlash®Rf 4X Organic Purification System [120 g RediSep® Normal-phase GOLD Silica Flash Column, dried loaded, elution gradient: 0→40% EtOAc in DCM] to afford 1.03 g (63% yield) of the desired product. 1H NMR (400 MHz, Chloroform-d) δ ppm 7.71 (d, J=8.08 Hz, 1 H), 7.45 (d, 1 H), 5.93-5.99 (m, 1 H), 4.20 (q, J=7.07 Hz, 2 H), 2.65-2.75 (m, 1 H), 2.49-2.56 (m, 2 H), 2.36-2.49 (m, 2 H), 2.16-2.24 (m, 1 H), 1.87-2.00 (m, 1 H), 1.54 (br. s., 3 H), 1.31 (t, J=7.20 Hz, 3 H). MS (ES+): m/z 346.15/347.15 (100/15) [MH+]. HPLC: tR=1.43 min (UPLC TOF, polar—3 min).

Workup

  1. customwas evacuated
  2. additionrefilled with Ar(g)((3×) and
  3. customirradiated in the microwave at 100° C. for 30 min
  4. concentrationThe crude mixture was concentrated in vacuo to a solid
  5. custompurified by CombiFlash®Rf 4X Organic Purification System [120 g RediSep® Normal-phase GOLD Silica Flash Column, dried loaded, elution gradient: 0→40% EtOAc in DCM]

Sources & evidence

ORD record
ord-7154095bd5cb4ebd965b7f5f05e372f8
Source dataset
uspto-grants-2015_08
Patent number
US09096624B2

Reaction notes

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