Pyridine → HCID 118069279, compound

HRID 920812Notes

Reaction equation

HRID 920812 reaction equation
[NH2:1][CH2:2][C@@H:3]([F:8])[C:4]([CH3:7])([OH:6])[CH3:5].Cl[C:10]([O:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)=[O:11].N1C=CC=CC=1>C(Cl)Cl>[C:13]1([O:12][C:10](=[O:11])[NH:1][CH2:2][C@@H:3]([F:8])[C:4]([OH:6])([CH3:7])[CH3:5])[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1

Participants

5

Reactant 3

HCID 1049PyridineHCID 15891Phenyl chloroformateHCID 90134281(R)-4-amino-3-fluoro-2-methylbutan-2-ol

Product 1

HCID 118069279HCID 118069279, compoundYield 65.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of (R)-4-amino-3-fluoro-2-methylbutan-2-ol (100 mg, 0.825 mmol) in DCM (3 mL) was added phenyl chloroformate (0.124 mL, 0.990 mmol) at 0° C. followed by pyridine (0.100 mL, 1.238 mmol); the reaction mixture was stirred at RT for 12 h. The reaction mixture was quenched with water and extracted with ethyl acetate (3×10 mL). The combined organic layer was washed with a 1.5 N aq. solution of HCl, dried over Na2SO4, filtered and the filtrate evaporated under vacuum to afford Intermediate 336A as a colorless liquid (130 mg, 65%). The crude product was used in the subsequent transformation without further purification. 1H NMR (300 MHz, chloroform-d) δ ppm 7.33-7.44 (m, 2H), 7.06-7.31 (m, 3H), 5.48 (bs, 1H), 4.30-4.56 (m, 1H), 3.73 (m, 1H), 3.33-3.51 (m, 1H), 1.91 (m, 1H), 1.32 (dd, J=11.95, 1.23 Hz, 6H).

Workup

  1. customThe reaction mixture was quenched with water
  2. extractionextracted with ethyl acetate (3×10 mL)
  3. washThe combined organic layer was washed with a 1.5 N aq. solution of HCl
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. customthe filtrate evaporated under vacuum

Sources & evidence

ORD record
ord-3ff40ea3ef744acba2b20c6c2e4ec206
Source dataset
uspto-grants-2016_03
Patent number
US09273058B2

Reaction notes

Loading…