Sodium Thiosulfate → 7-Amino-4-bromo-2-methylisoindolin-1-one

HRID 2279755Notes

Reaction equation

HRID 2279755 reaction equation
C1C(=O)N([Br:8])C(=O)C1.[NH2:9][C:10]1[CH:11]=[CH:12][CH:13]=[C:14]2[C:18]=1[C:17](=[O:19])[N:16]([CH3:20])[CH2:15]2.S([O-])([O-])(=O)=S.[Na+].[Na+]>C(Cl)Cl>[NH2:9][C:10]1[CH:11]=[CH:12][C:13]([Br:8])=[C:14]2[C:18]=1[C:17](=[O:19])[N:16]([CH3:20])[CH2:15]2

Participants

5

Reactant 3

HCID 24477Sodium ThiosulfateHCID 67184N-bromobutanimideHCID 450887127-Amino-2-methyl-2,3-dihydro-1H-isoindol-1-one2×

Product 1

HCID 534084597-Amino-4-bromo-2-methylisoindolin-1-oneYield 74%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

NBS (2.3 g, 12.96) was added to a cold (−8° C. to −10° C.) solution of 7-amino-2-methyl-2,3-dihydro-1H-isoindol-1-one (Compound 17E, 2 g, 12.4 mmol) in DCM (40 mL) and the mixture stirred at −8° C. to −10° C. for 1 h. A solution of 10% aq. sodium thiosulfate (30 mL) was then added to the reaction mixture and stirring was continued for another 20 minutes. The layers were separated and the aqueous layer was extracted with DCM (2×20 mL). The combined organic extracts were washed with water (3×40 mL) and brine (30 mL), and the organic layer was dried (Na2SO4) and concentrated in vacuo to yield 3.2 g of crude product. This material was triturated with ethyl acetate (10 mL) to give 2.2 g of pure 7-amino-4-bromo-2-methyl-2,3-dihydro-1H-isoindol-1-one (yield: 74%). 1H NMR (CDCl3 400 MHz): δ 3.14 (s, 3H), 4.20 (s, 2H), 5.20 (bs, 2H), 5.49 (d, 1H, J=8.4 Hz), 5.79 (d, 1H, J=8.4 Hz).

Workup

  1. stirringstirring
  2. waitwas continued for another 20 minutes
  3. customThe layers were separated
  4. extractionthe aqueous layer was extracted with DCM (2×20 mL)
  5. washThe combined organic extracts were washed with water (3×40 mL) and brine (30 mL)
  6. dry with materialthe organic layer was dried (Na2SO4)
  7. concentrationconcentrated in vacuo
  8. customto yield 3.2 g of crude product
  9. customThis material was triturated with ethyl acetate (10 mL)

Sources & evidence

ORD record
ord-585dea7479f242b4bae26060d5ff6e5e
Source dataset
uspto-grants-2015_09
Patent number
US09133224B2

Reaction notes

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