Hydrochloric Acid → HCID 86692748, compound

HRID 2403152Notes

Reaction equation

HRID 2403152 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][C@@H:12]2[CH2:14][C@H:9]1[C:10](=[O:15])[O:11]2)=[O:7])([CH3:4])([CH3:3])[CH3:2].Cl.[NH2:17][C:18]1([C:21]#[N:22])[CH2:20][CH2:19]1.C(C(CCCC)C([O-])=O)C.[Na+].Cl.[Cl-].[Na+]>O.C(OCC)(=O)C>[C:21]([C:18]1([NH:17][C:10]([C@@H:9]2[CH2:14][C@H:12]([OH:11])[CH2:13][N:8]2[C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:7])=[O:15])[CH2:20][CH2:19]1)#[N:22]

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 5234Sodium ChlorideHCID 11252852tert-Butyl (1S,4S)-3-oxo-2-oxa-5-azabicyclo[2.2.1]heptane-5-carboxylateHCID 145863631-Amino-1-cyclopropanecarbonitrile hydrochlorideHCID 23672331Sodium 2-ethylhexanoate

Product 1

HCID 86692748HCID 86692748, compoundYield 55.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
50 °C

Procedure

A suspension of tert-butyl 3-oxo-2-oxa-5-azabicyclo[2.2.1]heptane-5-carboxylate 8 (1 g, 4.69 mmol), 1-aminocyclopropanecarbonitrile hydrochloride (743 mg, 6.27 mmol) and sodium 2-ethylhexanoate (1.22 g, 7.12 mmol) in water (7 mL) was stirred for 2 days at 50° C. The reaction was acidified with 1N aqueous hydrogen chloride solution, saturated with sodium chloride and stirred with ethyl acetate for 1 hour. The organic layer was separated and the aqueous layer was extracted with ethyl acetate. The combined organic layers were washed with saturated aqueous sodium chloride solution, dried over Na2SO4, filtered and concentrated under reduced pressure. The residue was chromatographed on silica using a gradient of methylene chloride to a mixtures of methylene chloride and methanol (v:v 19:1) to yield the amide 9 as an off-white solid (763 mg, 55.1%). MS ISN (m/e): 294.3 (100) [(M−H)]+.

Workup

  1. customThe organic layer was separated
  2. extractionthe aqueous layer was extracted with ethyl acetate
  3. washThe combined organic layers were washed with saturated aqueous sodium chloride solution
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was chromatographed on silica using a gradient of methylene chloride to a mixtures of methylene chloride and methanol (v:v 19:1)

Sources & evidence

ORD record
ord-2146f534070c4109b87f17c17bee5821
Source dataset
uspto-grants-2014_08
Patent number
US08802665B2

Reaction notes

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