Acetic Acid → (S)-1-(Tetrahydro-pyran-4-yl)-azetidine-2-carboxylic acid (3-tert-butyl-isoxazol-5-yl)-amide

HRID 389860Notes

Reaction equation

HRID 389860 reaction equation
[C:1]([C:5]1[CH:9]=[C:8]([NH:10][C:11]([C@@H:13]2[CH2:16][CH2:15][NH:14]2)=[O:12])[O:7][N:6]=1)([CH3:4])([CH3:3])[CH3:2].Cl.[O:18]1[CH2:23][CH2:22][C:21](=O)[CH2:20][CH2:19]1.C(O)(=O)C.C([BH3-])#N.[Na+]>CN(C=O)C>[C:1]([C:5]1[CH:9]=[C:8]([NH:10][C:11]([C@@H:13]2[CH2:16][CH2:15][N:14]2[CH:21]2[CH2:22][CH2:23][O:18][CH2:19][CH2:20]2)=[O:12])[O:7][N:6]=1)([CH3:4])([CH3:2])[CH3:3]

Participants

7

Reactant 5

HCID 176Acetic AcidHCID 313Hydrochloric AcidHCID 121599Tetrahydro-4H-pyran-4-oneHCID 5003444Sodium cyanoborohydrideHCID 67953683(S)-Azetidine-2-carboxylic acid (3-tert-butyl-isoxazol-5-yl)-amide

Product 1

HCID 49847677(S)-1-(Tetrahydro-pyran-4-yl)-azetidine-2-carboxylic acid (3-tert-butyl-isoxazol-5-yl)-amide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of (S)-Azetidine-2-carboxylic acid (3-tert-butyl-isoxazol-5-yl)-amide; hydrochloride (78.6 mg; 0.303 mol) in DMF (1 mL) is added tetrahydro-4H-pyran-4-one (0.056 mL; 0.606 mmol) and acetic acid (0.069 mL; 1.212 mmol). The reaction is stirred at room temperature for 50 minutes before adding sodium cyanoborohydride (57 mg; 0.909 mmol). The reaction mixture is left stifling at room temperature for 18 hours. After this time, the reaction mixture is quenched with saturated sodium bicarbonate aqueous solution and extracted with ethyl acetate twice. The organics are combined and washed with brine, dried over Na2SO4, filtered and concentrated in vacuo. Purification by flash chromatography on silica gel using methanol/methylene chloride provides the title compound, m/z 308 [M+H+].

Workup

  1. waitThe reaction mixture is left
  2. waitstifling at room temperature for 18 hours
  3. customAfter this time, the reaction mixture is quenched with saturated sodium bicarbonate aqueous solution
  4. extractionextracted with ethyl acetate twice
  5. washwashed with brine
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customPurification by flash chromatography on silica gel

Sources & evidence

ORD record
ord-8c09f9cb31b24669a451f1169a1a5fa9
Source dataset
uspto-grants-2013_02
Patent number
US08383615B2

Reaction notes

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