Acetic Acid → HCID 68662630, compound

HRID 888983Notes

Reaction equation

HRID 888983 reaction equation
[C:1]1(=[O:13])[CH:9]2[CH:4]([CH:5]3[CH2:10][CH:8]2[CH2:7][C:6]3=[O:11])[C:3](=[O:12])[NH:2]1.[CH3:14][Mg]Br.C(O)(=O)C.O>C1COCC1.C(Cl)Cl.CO.CO.C(Cl)Cl>[OH:11][C:6]1([CH3:14])[CH2:7][CH:8]2[CH2:10][CH:5]1[CH:4]1[CH:9]2[C:1](=[O:13])[NH:2][C:3]1=[O:12]

Participants

9

Reactant 4

HCID 176Acetic AcidHCID 962WaterHCID 58279940HCID 58279940, compoundHCID 178418573HCID 178418573, compound3×

Product 1

HCID 68662630HCID 68662630, compound

Reagents, catalysts & solvents 4

HCID 887MethanolSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent2×HCID 21226129Dichloromethane methanolSolvent

Procedure

To a −78° C. solution of rac-(3aS,4S,7S,7aR)-tetrahydro-1H-4,7-methanoisoindole-1,3,5(4H)-trione (1.08 g, 6.03 mmol) (Kossakowski, Jerzy; Zawadowski, Teodor; Balicka, Eliza., Acta Poloniae Pharmaceutica (1997), 54(6), 479-481) in 50 ml of anhydrous THF was added methylmagnesium bromide (5.02 ml of a 3 M solution in THF, 15.07 mmol). After 2 hr, an additional 3 mL of methylmagnesium bromide solution was added. After another 2 hr, an additional 2 mL of methylmagnesium bromide solution was added. After 6 hr total at −78° C., the cooling bath was removed and the reaction allowed to warm to room temperature. The reaction was quenched with acetic acid (1.725 ml, 30.1 mmol) (Carefully). 200 uL of water was added, and the mixture was diluted with CH2Cl2 and 2 mL MeOH. The mixture was dried over Na2SO4, filtered, and concentrated to give a white foam. The foam was dissolved in 5% MeOH/CH2Cl2 and filtered through a plug of silica to give the titled compound as an off-white solid.

Workup

  1. waitAfter another 2 hr
  2. waitAfter 6 hr total at −78° C.
  3. customthe cooling bath was removed
  4. dry with materialThe mixture was dried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customto give a white foam
  8. filtrationfiltered through a plug of silica

Sources & evidence

ORD record
ord-04749dbdce9a43508497c1b8c2766b30
Source dataset
uspto-grants-2012_08
Patent number
US08252799B2

Reaction notes

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