Acetic Acid → HCID 67459256, compound

HRID 469737Notes

Reaction equation

HRID 469737 reaction equation
[C:1]([C:5]1[O:9][N:8]=[C:7]([NH:10][C:11]([C@@H:13]2[CH2:17][C@@H:16]([OH:18])[CH2:15][NH:14]2)=[O:12])[CH:6]=1)([CH3:4])([CH3:3])[CH3:2].Cl.[O:20]1[CH2:25][CH2:24][CH:23]([CH:26]=O)[CH2:22][CH2:21]1.C(O)(=O)C.C([BH3-])#N.[Na+]>CN(C)C=O>[C:1]([C:5]1[O:9][N:8]=[C:7]([NH:10][C:11]([C@@H:13]2[CH2:17][C@@H:16]([OH:18])[CH2:15][N:14]2[CH2:26][CH:23]2[CH2:24][CH2:25][O:20][CH2:21][CH2:22]2)=[O:12])[CH:6]=1)([CH3:4])([CH3:2])[CH3:3]

Participants

7

Reactant 5

HCID 176Acetic AcidHCID 313Hydrochloric AcidHCID 5003444Sodium cyanoborohydrideHCID 9964078Tetrahydro-2H-pyran-4-carboxaldehydeHCID 67953452HCID 67953452, compound

Product 1

HCID 67459256HCID 67459256, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of (2S,4R)-4-hydroxy-pyrrolidine-2-carboxylic acid (5-tert-butyl-isoxazol-3-yl)-amide; hydrochloride (100 mg, 0.338 mmol) in N,N-dimethylformamide (2 mL) is added tetrahydro-pyran-4-carbaldehyde (77 mg, 0.676 mmol) and acetic acid (0.073 mL, 1.28 mmol). The reaction is stirred at room temperature for 45 minutes before adding sodium cyanoborohydride (42.5 mg, 0.676 mmol). The reaction is stirred at room temperature overnight. The reaction 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 under reduced pressure. Purification by chromatography on silica eluting with methanol/dichloromethane provides the title compound with low purity and further purification by pre-HPLC yields pure title compound, m/z 352 [M+H+].

Workup

  1. stirringThe reaction is stirred at room temperature overnight
  2. customThe reaction is quenched with saturated sodium bicarbonate aqueous solution
  3. extractionextracted with ethyl acetate twice
  4. washwashed with brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customPurification by chromatography on silica eluting with methanol/dichloromethane

Sources & evidence

ORD record
ord-e4e39b8360fa412286c0e1367f6aa144
Source dataset
uspto-grants-2014_01
Patent number
US08629157B2

Reaction notes

Loading…