Nitrogen → 2,5-Di-tert-butyl-3-hydroxyisoindolin-1-one

HRID 337286Notes

Reaction equation

HRID 337286 reaction equation
N#N.[C:3]([NH:7][C:8](=[O:19])[C:9]1[CH:14]=[CH:13][C:12]([C:15]([CH3:18])([CH3:17])[CH3:16])=[CH:11][CH:10]=1)([CH3:6])([CH3:5])[CH3:4].C([Li])(CC)C.CN([CH:28]=[O:29])C.[NH4+].[Cl-]>O.C1COCC1>[C:3]([N:7]1[CH:28]([OH:29])[C:10]2[C:9](=[CH:14][CH:13]=[C:12]([C:15]([CH3:18])([CH3:17])[CH3:16])[CH:11]=2)[C:8]1=[O:19])([CH3:6])([CH3:5])[CH3:4]

Participants

8

Reactant 5

HCID 947Nitrogen2×HCID 6228DimethylformamideHCID 25517Ammonium ChlorideHCID 349124N,4-di-tert-butylbenzamideHCID 178418400CID 53628100

Product 1

HCID 712578022,5-Di-tert-butyl-3-hydroxyisoindolin-1-oneYield 88%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

In a 1 L three-necked flask fitted with an addition funnel with line to a bubbler, and a nitrogen inlet, that was purged with N2, N,4-di-tert-butylbenzamide (5 g, 21.4 mmol, Eq: 1.00) was combined with THF (200 ml) to give a light yellow solution. The reaction was cooled to −78° C. The sec-butyllithium in cyclohexanes (31.4 ml of 1.4 M, 43.9 mmol, Eq: 2.05) was added dropwise slowly and with a stream of N2. A yellow solution resulted. The reaction mixture was warmed to −15° C. for 1 h. A pale yellow suspension resulted. The reaction mixture was cooled back down to −78° C. Dry DMF (3.13 g, 3.32 ml, 42.9 mmol, Eq: 2) was added dropwise. The reaction mixture was allowed to warm to room temperature. 30 mL of saturated NH4Cl was added slowly at 0° C. The reaction mixture was poured into 150 mL H2O and extracted with EtOAc (3×250 mL). The combined organic extracts were washed with brine, dried over MgSO4 and concentrated in vacuo. The crude material was purified by flash chromatography (silica gel, 80 g, 0% to 40% EtOAc in hexanes to afford the desired product (4.9 g, 88% yield). (M+H)+=262 m/e.

Workup

  1. customIn a 1 L three-necked flask fitted with an addition funnel with line to a bubbler, and a nitrogen inlet
  2. customto give a light yellow solution
  3. customA yellow solution resulted
  4. temperatureThe reaction mixture was warmed to −15° C. for 1 h
  5. customA pale yellow suspension resulted
  6. temperatureThe reaction mixture was cooled back down to −78° C
  7. temperatureto warm to room temperature
  8. extractionextracted with EtOAc (3×250 mL)
  9. washThe combined organic extracts were washed with brine
  10. dry with materialdried over MgSO4
  11. concentrationconcentrated in vacuo
  12. customThe crude material was purified by flash chromatography (silica gel, 80 g, 0% to 40% EtOAc in hexanes

Sources & evidence

ORD record
ord-71147adfa18d4a30b6559bccd36de333
Source dataset
uspto-grants-2014_11
Patent number
US08889682B2

Reaction notes

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