Hydrochloric Acid → Ethyl 4-((tert-butoxycarbonyl)amino)-2-cyano-2-cyclopropylbutanoate

HRID 714813Notes

Reaction equation

HRID 714813 reaction equation
[C:1]([CH:3]([CH:9]1[CH2:11][CH2:10]1)[C:4]([O:6][CH2:7][CH3:8])=[O:5])#[N:2].C(=O)([O-])[O-].[Cs+].[Cs+].O1[CH2:22][CH2:21][N:20]([C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])S1(=O)=O.Cl>C1(C)C=CC=CC=1.[Br-].C([N+](CCCC)(CCCC)CCCC)CCC>[C:26]([O:25][C:23]([NH:20][CH2:21][CH2:22][C:3]([C:1]#[N:2])([CH:9]1[CH2:10][CH2:11]1)[C:4]([O:6][CH2:7][CH3:8])=[O:5])=[O:24])([CH3:29])([CH3:28])[CH3:27]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 10796Cesium carbonateHCID 10606956Ethyl 2-cyano-2-cyclopropylacetateHCID 235840203-Boc-1,2,3-oxathiazolidine 2,2-dioxide

Product 1

HCID 117840908Ethyl 4-((tert-butoxycarbonyl)amino)-2-cyano-2-cyclopropylbutanoateYield 86.1%

Reagents, catalysts & solvents 2

HCID 74236Tetrabutylammonium BromideCatalystHCID 1140TolueneSolvent

Procedure

To a solution of ethyl cyano(cyclopropyl)acetate (27 g) obtained in Step A of Example 103 in toluene (400 mL) were added cesium carbonate (88 g), tetrabutylammonium bromide (5.8 g) and tert-butyl 1,2,3-oxathiazolidine-3-carboxylate 2,2-dioxide (40 g), and the mixture was stirred overnight at room temperature. The reaction mixture was neutralized with 0.5 M hydrochloric acid (400 mL), and extracted with ethyl acetate. The obtained organic layer was washed successively with water and saturated brine, and dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate) to give the title compound (45 g).

Workup

  1. extractionextracted with ethyl acetate
  2. washThe obtained organic layer was washed successively with water and saturated brine
  3. dry with materialdried over anhydrous magnesium sulfate
  4. customthe solvent was evaporated under reduced pressure
  5. customThe residue was purified by silica gel column chromatography (hexane/ethyl acetate)

Sources & evidence

ORD record
ord-8c0fca8095dd405eb0b9d66cbaa1593e
Source dataset
uspto-grants-2015_11
Patent number
US09187453B2

Reaction notes

Loading…