tert-Butanol → HCID 90132491, compound

HRID 2275787Notes

Reaction equation

HRID 2275787 reaction equation
[O:1]=[C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[C:4](=[O:11])[N:3]1[CH:12]([C:17]1[CH:22]=[CH:21][C:20]([F:23])=[CH:19][CH:18]=1)[CH2:13]C(O)=O.C(N(CC)CC)C.[N:31]12[CH2:38]CN(CC1)CC2.C1(P(N=[N+]=[N-])(C2C=CC=CC=2)=[O:46])C=CC=CC=1.[C:56]([OH:60])([CH3:59])([CH3:58])[CH3:57]>C1(C)C=CC=CC=1.C(OCC)(=O)C>[O:1]=[C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[C:4](=[O:11])[N:3]1[CH:12]([C:17]1[CH:22]=[CH:21][C:20]([F:23])=[CH:19][CH:18]=1)[CH2:13][NH:31][C:38](=[O:46])[O:60][C:56]([CH3:59])([CH3:58])[CH3:57]

Participants

8

Reactant 5

HCID 6386tert-ButanolHCID 8471TriethylamineHCID 9237DabcoHCID 199401P,P-Diphenylphosphinic azideHCID 3816170HCID 3816170, compound

Product 1

HCID 90132491HCID 90132491, compound

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Procedure

Under argon, a solution of 3.2 g of rac-3-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-3-(4-fluorophenyl)propanoic acid (Example 47A, 8.78 mmol) in 32 ml of toluene was initially charged, and 1.33 g of triethylamine (13.18 mmol), 98 mg of 1,4-diazabicyclo[2.2.2]octane (0.88 mmol), 3.14 g of diphenylphosphoryl azide (11.42 mmol) and 6.51 g of tert-butanol (87.84 mmol) were added. The reaction mixture was heated at reflux overnight and then diluted with ethyl acetate and washed with water. The organic phase was dried over sodium sulphate, filtered and concentrated. The crude product was purified by silica gel chromatography (mobile phase: cyclohexane/ethyl acetate 8:1; 6:1). This gave 959 mg of the title compound (28% of theory).

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureat reflux overnight
  3. washwashed with water
  4. dry with materialThe organic phase was dried over sodium sulphate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe crude product was purified by silica gel chromatography (mobile phase: cyclohexane/ethyl acetate 8:1; 6:1)

Sources & evidence

ORD record
ord-bebad59cf44442a883d375d9d7e67674
Source dataset
uspto-grants-2015_09
Patent number
US09126998B2

Reaction notes

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