Isopropyl chloroformate → HCID 131729851, compound

HRID 1517346Notes

Reaction equation

HRID 1517346 reaction equation
[CH3:1][C@H:2]1[CH2:7][C@@H:6]([O:8][C:9]2[CH:14]=[C:13]([N:15]3[C:23]4[C:18](=[CH:19][C:20]([S:24]([CH3:27])(=[O:26])=[O:25])=[CH:21][CH:22]=4)[CH2:17][CH2:16]3)[N:12]=[CH:11][N:10]=2)[CH2:5][CH2:4][N:3]1[C:28]([O:30][CH2:31][C:32]1C=CC=CC=1)=[O:29].[H][H].[CH:40](N(C(C)C)CC)(C)C.ClC(OC(C)C)=O.[Cl-].[NH4+]>[OH-].[Pd+2].[OH-].ClCCl.C(OCC)(=O)C.CO>[CH3:1][C@H:2]1[CH2:7][C@@H:6]([O:8][C:9]2[CH:14]=[C:13]([N:15]3[C:23]4[C:18](=[CH:19][C:20]([S:24]([CH3:27])(=[O:25])=[O:26])=[CH:21][CH:22]=4)[CH2:17][CH2:16]3)[N:12]=[CH:11][N:10]=2)[CH2:5][CH2:4][N:3]1[C:28]([O:30][CH:31]([CH3:40])[CH3:32])=[O:29]

Participants

10

Reactant 5

HCID 7917Isopropyl chloroformateHCID 25517Ammonium ChlorideHCID 81531DiisopropylethylamineHCID 131729852HCID 131729852, compoundHCID 178418361HCID 178418361, compound

Product 1

HCID 131729851HCID 131729851, compoundYield 16.2%

Reagents, catalysts & solvents 4

HCID 9942167Palladium hydroxideCatalystHCID 887MethanolSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

Palladium hydroxide (300 mg) was added to a methanol (5 mL)/ethyl acetate (5 mL) mixed solution of the benzyl rac-cis-2-methyl-4-({6-[5-(methylsulfonyl)indolin-1-yl]pyrimidin-4-yl}oxy)piperidine-1-carboxylate (271 mg, 0.519 mmol) produced in Example 112, and the mixture was stirred for 2 hours in a hydrogen atmosphere. The reaction solution was filtered through Celite (trade name), and the solvent was distilled off under reduced pressure. To a dichloromethane (10 mL) solution of the obtained residue, diisopropylethylamine (447 μL, 2.63 mmol) and isopropyl chloroformate (218 μL, 1.56 mmol) were added at 0° C., and the mixture was stirred for 30 minutes with heating to room temperature. To the reaction solution, a saturated aqueous solution of ammonium chloride was added, followed by extraction with ethyl acetate three times. The obtained organic layer was dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. The obtained residue was purified by silica gel column chromatography (hexane:ethyl acetate=7:3-3:2, V/V) to obtain the title compound as white powder (39.8 mg, yield: 16%).

Workup

  1. filtrationThe reaction solution was filtered through Celite (trade name)
  2. distillationthe solvent was distilled off under reduced pressure
  3. extractionfollowed by extraction with ethyl acetate three times
  4. dry with materialThe obtained organic layer was dried over anhydrous sodium sulfate
  5. distillationthe solvent was distilled off under reduced pressure
  6. customThe obtained residue was purified by silica gel column chromatography (hexane:ethyl acetate=7:3-3:2, V/V)

Sources & evidence

ORD record
ord-528e5be390324842a24adb0ae624dac2
Source dataset
uspto-grants-2012_07
Patent number
US08232287B2

Reaction notes

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