Methyl chloroformate → HCID 67992236, compound

HRID 2046147Notes

Reaction equation

HRID 2046147 reaction equation
C(NC(C)C)(C)C.[Li]CCCC.[CH:13]1[CH:14]=[C:15]([N:21]2[CH2:26][CH2:25][N:24]([CH2:27][CH2:28][CH2:29][CH2:30][O:31][C:32]3[CH:33]=[CH:34][C:35]4[CH2:42][CH2:41][C:39](=[O:40])[NH:38][C:36]=4[CH:37]=3)[CH2:23][CH2:22]2)[C:16]([Cl:20])=[C:17]([Cl:19])[CH:18]=1.[CH3:43][O:44][C:45](Cl)=[O:46]>CC1CCCO1>[Cl:20][C:16]1[C:17]([Cl:19])=[CH:18][CH:13]=[CH:14][C:15]=1[N:21]1[CH2:26][CH2:25][N:24]([CH2:27][CH2:28][CH2:29][CH2:30][O:31][C:32]2[CH:37]=[C:36]3[C:35]([CH2:42][CH2:41][C:39](=[O:40])[N:38]3[C:45]([O:44][CH3:43])=[O:46])=[CH:34][CH:33]=2)[CH2:23][CH2:22]1

Participants

6

Reactant 4

HCID 6586Methyl chloroformateHCID 7912DiisopropylamineHCID 60795AripiprazoleHCID 178418339Butyllithium

Product 1

HCID 67992236HCID 67992236, compound

Reagents, catalysts & solvents 1

HCID 73012-MethyltetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

To a solution of diisopropylamine (0.99 mL, 7.02 mmol) in 2-methyltetrahydrofuran (33 mL) at −5° C. was added n-BuLi (2.67 mL, 2.5 M in hexanes, 6.69 mmol) slowly. After 20 minutes, the reaction was cooled to −78° C. and aripiprazole (1.50 g, 3.34 mmol) was added. After a further 10 minutes, methylchloroformate (0.65 mL, 8.36 mmol) was added. The reaction was held at −78° C. for 2 hours before allowing to warm to room temperature. After 2 hours the reaction was quenched with saturated aqueous ammonium chloride solution (30 mL) and extracted with ethyl acetate (2×30 mL). The organics were combined, washed with saturated aqueous sodium hydrogen carbonate solution (30 mL), brine (30 mL), dried over MgSO4 and concentrated. The crude product was purified by column chromatography on silica eluting with 1:1 ethyl acetate to dichloromethane to 10% methanol in 1:1 ethyl acetate to dichloromethane to give the product. The product was triturated in heptane to remove aliphatic impurities and then filtered to afford Compound-74 (0.824 g) as a colorless solid.

Workup

  1. waitAfter a further 10 minutes
  2. waitThe reaction was held at −78° C. for 2 hours
  3. temperatureto warm to room temperature
  4. customAfter 2 hours the reaction was quenched with saturated aqueous ammonium chloride solution (30 mL)
  5. extractionextracted with ethyl acetate (2×30 mL)
  6. washwashed with saturated aqueous sodium hydrogen carbonate solution (30 mL), brine (30 mL)
  7. dry with materialdried over MgSO4
  8. concentrationconcentrated
  9. customThe crude product was purified by column chromatography on silica eluting with 1:1 ethyl acetate to dichloromethane to 10% methanol in 1:1 ethyl acetate to dichloromethane
  10. customto give the product
  11. customThe product was triturated in heptane
  12. customto remove aliphatic impurities
  13. filtrationfiltered
  14. customto afford Compound-74 (0.824 g) as a colorless solid

Sources & evidence

ORD record
ord-88147804eb8e41508909dcd05edb3d84
Source dataset
uspto-grants-2013_11
Patent number
US08592427B2

Reaction notes

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