Hydrogen Bromide → 2-(4-Bromo-3-oxobutyl)-1H-isoindole-1,3(2H)-dione

HRID 2087092Notes

Reaction equation

HRID 2087092 reaction equation
[C:1](Cl)(=O)C(Cl)=O.[CH:7]1[CH:12]=[C:11]2[C:13]([N:15]([CH2:18][CH2:19][C:20]([OH:22])=O)[C:16](=[O:17])[C:10]2=[CH:9][CH:8]=1)=[O:14].C[Si](C=[N+]=[N-])(C)C.CCCCCC.[BrH:36].C(=O)(O)[O-].[Na+]>ClCCl.CN(C)C=O.C(#N)C.O1CCCC1>[Br:36][CH2:1][C:20](=[O:22])[CH2:19][CH2:18][N:15]1[C:16](=[O:17])[C:10]2[C:11](=[CH:12][CH:7]=[CH:8][CH:9]=2)[C:13]1=[O:14]

Participants

11

Reactant 6

HCID 260Hydrogen BromideHCID 8058HexaneHCID 65578Oxalyl chlorideHCID 768593-Phthalimidopropionic acidHCID 167693TrimethylsilyldiazomethaneHCID 516892Sodium Bicarbonate

Product 1

HCID 37597442-(4-Bromo-3-oxobutyl)-1H-isoindole-1,3(2H)-dioneYield 86%

Reagents, catalysts & solvents 4

HCID 6228DimethylformamideCatalystHCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolvent2×HCID 8028TetrahydrofuranSolvent

Procedure

Oxalyl chloride (5.8 ml; 66.7 mmol) is added to Pht-β-Ala-OH (9.96 g; 44.5 mmol) dissolved in dichloromethane (120 ml) and 3 drops of dimethylformamide (DMF). The mixture is stirred for 3 hours at ambient temperature. After elimination of the solvent, the white solid is taken up in a 1:1 mixture of anhydrous tetrahydrofuran and acetonitrile (200 ml) then 49 ml of a 2 M solution of (trimethylsilyl) diazomethane in hexane (97.9 mmol) are added dropwise at 0° C. The solvents are eliminated after one night of stirring at 0° C. The pale yellow solid is then dissolved in dichloromethane (60 ml) and 12 ml of aqueous hydrobromic acid (48%) is added dropwise at 0° C. The mixture is stirred until the temperature reaches 15° C. and 50 ml of a saturated solution of sodium bicarbonate is added. The organic phase is washed with salt water then dried over sodium sulphate. Crystallization from diethyl ether allows a white solid to be obtained (11.39 g; yield=86%).

Workup

  1. waitThe solvents are eliminated after one night
  2. stirringof stirring at 0° C
  3. stirringThe mixture is stirred until the temperature
  4. customreaches 15° C.
  5. washThe organic phase is washed with salt water
  6. dry with materialthen dried over sodium sulphate
  7. customCrystallization from diethyl ether
  8. customto be obtained (11.39 g; yield=86%)

Sources & evidence

ORD record
ord-09a30eff4f454a359748655f1454dcc8
Source dataset
uspto-grants-2004_04
Patent number
US06727269B1

Reaction notes

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