Phthalimide → HCID 21949773, compound

HRID 558294Notes

Reaction equation

HRID 558294 reaction equation
[CH2:1]([C:3]1[C:7]([O:8][C:9]2[CH:10]=[C:11]([CH:15]=[C:16]([F:18])[CH:17]=2)[C:12]([NH2:14])=[O:13])=[C:6]([CH2:19][CH3:20])[N:5]([CH2:21][CH2:22]O)[N:4]=1)[CH3:2].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(=O)[NH:47]C(=O)C2=CC=CC=C12.CC(OC(/N=N/C(OC(C)C)=O)=O)C.O.NN>O1CCCC1>[NH3:4].[NH2:47][CH2:22][CH2:21][N:5]1[C:6]([CH2:19][CH3:20])=[C:7]([O:8][C:9]2[CH:10]=[C:11]([CH:15]=[C:16]([F:18])[CH:17]=2)[C:12]([NH2:14])=[O:13])[C:3]([CH2:1][CH3:2])=[N:4]1

Participants

8

Reactant 5

HCID 6809PhthalimideHCID 11776TriphenylphosphineHCID 24654Hydrazine hydrate (1:1)HCID 5363146Diisopropyl azodicarboxylateHCID 21949930HCID 21949930, compound

Product 2

HCID 222AmmoniaHCID 21949773HCID 21949773, compoundYield 85.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

The alcohol from Example 163 (142 mg, 0.44 mmol), triphenylphosphine (346 mg, 1.32 mmol) and phthalimide (194 mg, 1.32 mmol) were dissolved in tetrahydrofuran (8 ml) at 0° C. under nitrogen and diisopropylazodicarboxylate (260 μl, 1.32 mmol) dissolved in tetrahydrofuran (1 ml) was added over 10 minutes. The reaction was allowed to warm to room temperature and was stirred for 18 hours. The solvent was removed under reduced pressure, the residue was dissolved in ethanol (9 ml) and hydrazine hydrate (107 μl, 2.2 mmol) was added. The slurry was stirred for 4 hours at 45° C. under nitrogen, concentrated under reduced pressure and the residue was dissolved in methanol. The solution was then passed through a polymer supported sulphonic acid column eluting with methanol to remove impurities, then 2M methanolic ammonia solution to elute the product. The product was then purified by flash chromatography on alumina eluting with dichloromethane:methanol:0.88 ammonia (90:10:1, by volume) to provide the title compound (60 mg) as an oil.

Workup

  1. additionwas added over 10 minutes
  2. customThe solvent was removed under reduced pressure
  3. dissolutionthe residue was dissolved in ethanol (9 ml)
  4. stirringThe slurry was stirred for 4 hours at 45° C. under nitrogen
  5. concentrationconcentrated under reduced pressure
  6. dissolutionthe residue was dissolved in methanol
  7. washeluting with methanol
  8. customto remove impurities
  9. wash2M methanolic ammonia solution to elute the product
  10. customThe product was then purified by flash chromatography on alumina eluting with dichloromethane

Sources & evidence

ORD record
ord-b21456f494b048698a50954d008dad9f
Source dataset
uspto-grants-2011_11
Patent number
US08063044B2

Reaction notes

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