Hydrochloric Acid → 2,2-Dimethyl-propionic acid 3-(4'-chloro-6-fluoro-4-methyl-biphenyl-3-yl)-8-methoxy-2-oxo-1,8-diaza-spiro[4.5]dec-3-en-4-yl ester

HRID 1022390Notes

Reaction equation

HRID 1022390 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:13]([F:14])=[CH:12][C:11]([CH3:15])=[C:10]([C:16]3[C:17](=[O:29])[NH:18][C:19]4([CH2:26][CH2:25][N:24]([O:27][CH3:28])[CH2:23][CH2:22]4)[C:20]=3[OH:21])[CH:9]=2)=[CH:4][CH:3]=1.[C:30](Cl)(=[O:35])[C:31]([CH3:34])([CH3:33])[CH3:32].N1C=CC=CC=1.Cl>C(#N)C>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:13]([F:14])=[CH:12][C:11]([CH3:15])=[C:10]([C:16]3[C:17](=[O:29])[NH:18][C:19]4([CH2:22][CH2:23][N:24]([O:27][CH3:28])[CH2:25][CH2:26]4)[C:20]=3[O:21][C:30](=[O:35])[C:31]([CH3:34])([CH3:33])[CH3:32])[CH:9]=2)=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 1049PyridineHCID 62493Pivaloyl chlorideHCID 596145833-(4'-Chloro-6-fluoro-4-methyl-biphenyl-3-yl)-4-hydroxy-8-methoxy-1,8-diazaspiro[4.5]dec-3-en-2-one

Product 1

HCID 580312202,2-Dimethyl-propionic acid 3-(4'-chloro-6-fluoro-4-methyl-biphenyl-3-yl)-8-methoxy-2-oxo-1,8-diaza-spiro[4.5]dec-3-en-4-yl ester

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a solution of 3-(4′-chloro-6-fluoro-4-methyl-biphenyl-3-yl)-4-hydroxy-8-methoxy-1,8-diaza-spiro[4.5]dec-3-en-2-one (170 mg) and pivaloyl chloride (98 mg) in acetonitrile (5 ml) is added pyridine (64 mg) and the reaction mixture stirred at room temperature for 8 hours. The mixture is poured on diluted HCl and extracted with ethyl acetate (3×). The combined organic layers are washed with brine, dried over sodium sulfate and concentrated. The residue is triturated with heptane, filtered and dried. Yield: 100 mg of 2,2-dimethyl-propionic acid 3-(4′-chloro-6-fluoro-4-methyl-biphenyl-3-yl)-8-methoxy-2-oxo-1,8-diaza-spiro[4.5]dec-3-en-4-yl ester as a solid, mp: 150-151° C.

Workup

  1. extractionextracted with ethyl acetate (3×)
  2. washThe combined organic layers are washed with brine
  3. dry with materialdried over sodium sulfate
  4. concentrationconcentrated
  5. customThe residue is triturated with heptane
  6. filtrationfiltered
  7. customdried

Sources & evidence

ORD record
ord-e81de93d7c2f4ec1bd8d810277f91fa8
Source dataset
uspto-grants-2014_05
Patent number
US08722578B2

Reaction notes

Loading…