Hydrochloric Acid → 6-Chloro-2,3-dihydro-2-methyl-5-nitro-1H-isoindol-1-one

HRID 2401468Notes

Reaction equation

HRID 2401468 reaction equation
Br[CH2:2][C:3]1[CH:12]=[C:11]([N+:13]([O-:15])=[O:14])[C:10]([Cl:16])=[CH:9][C:4]=1[C:5](OC)=[O:6].C[CH2:18][N:19](CC)CC.CN.CCO.Cl>CO.CCOC(C)=O>[Cl:16][C:10]1[CH:9]=[C:4]2[C:3]([CH2:2][N:19]([CH3:18])[C:5]2=[O:6])=[CH:12][C:11]=1[N+:13]([O-:15])=[O:14]

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 702EthanolHCID 6329MethylamineHCID 8471TriethylamineHCID 71744076Methyl 2-(bromomethyl)-5-chloro-4-nitrobenzoate

Product 1

HCID 866879266-Chloro-2,3-dihydro-2-methyl-5-nitro-1H-isoindol-1-oneYield 77%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
70 °C

Procedure

To methyl 2-(bromomethyl)-5-chloro-4-nitrobenzoate (617 mg, 2 mmol) in methanol (18 mL) was added Et3N (0.34 mL, 2.4 mmol) and methylamine in EtOH (0.3 mL, ˜d 8 M in EtOH, 2.4 mmol). The mixture was heated to 70° C. for 3 h. and then EtOAc (30 mL) and 2M HCl(aq) (30 mL) was added. The layers were separated and the aqueous layer was extracted with EtOAc (2×30 mL). The combined organic fractions were passed through a hydrophobic frit and the solvent was removed in vacuo. Purification of the residue via silica gel column chromatography (0-10% methanol in DCM) gave 6-chloro-2-methyl-5-nitroisoindolin-1-one (347 mg, 77%) as an off-white solid. LCMS (10 cm_ESCI_Bicarb_MeCN): [M+H]+=227 at 2.89 min. 1H NMR (400 MHz, CDCl3): δ 8.00 (s, 1H), 7.90 (s, 1H), 4.46 (s, 2H), 3.24 (s, 3H).

Workup

  1. customThe layers were separated
  2. extractionthe aqueous layer was extracted with EtOAc (2×30 mL)
  3. customthe solvent was removed in vacuo
  4. customPurification of the residue via silica gel column chromatography (0-10% methanol in DCM)

Sources & evidence

ORD record
ord-e5afa7a4a65b42c08c6c5add827b3057
Source dataset
uspto-grants-2014_08
Patent number
US08796296B2

Reaction notes

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