m-Chloroperbenzoic acid → HCID 24999761, compound

HRID 424139Notes

Reaction equation

HRID 424139 reaction equation
[C:1]([C:5]1[CH:9]=[C:8]([NH:10][C:11]([NH:13][C:14]2[CH:30]=[CH:29][C:17]([O:18][C:19]3[CH:24]=[CH:23][N:22]=[C:21]([C:25]([NH:27][CH3:28])=[O:26])[CH:20]=3)=[CH:16][C:15]=2[F:31])=[O:12])[N:7]([C:32]2[CH:37]=[CH:36][CH:35]=[C:34]([CH2:38][OH:39])[CH:33]=2)[N:6]=1)([CH3:4])([CH3:3])[CH3:2].C(N(CC)[P:43]([O:49][C:50]([CH3:53])([CH3:52])[CH3:51])[O:44][C:45]([CH3:48])([CH3:47])[CH3:46])C.ClC1C=C(C=CC=1)C(OO)=[O:61]>OS([O-])=O.[Na+]>[P:43]([O:39][CH2:38][C:34]1[CH:35]=[CH:36][CH:37]=[C:32]([N:7]2[C:8]([NH:10][C:11](=[O:12])[NH:13][C:14]3[CH:30]=[CH:29][C:17]([O:18][C:19]4[CH:24]=[CH:23][N:22]=[C:21]([C:25](=[O:26])[NH:27][CH3:28])[CH:20]=4)=[CH:16][C:15]=3[F:31])=[CH:9][C:5]([C:1]([CH3:4])([CH3:2])[CH3:3])=[N:6]2)[CH:33]=1)([O:44][C:45]([CH3:46])([CH3:47])[CH3:48])([O:49][C:50]([CH3:51])([CH3:52])[CH3:53])=[O:61]

Participants

5

Reactant 3

HCID 70297m-Chloroperbenzoic acidHCID 4251849Di-tert-butyl diethylphosphoramiditeHCID 24829325HCID 24829325, compound

Product 1

HCID 24999761HCID 24999761, compoundYield 58.3%

Reagents, catalysts & solvents 1

HCID 23665763Sodium BisulfiteSolvent

Procedure

To a room temperature solution of 1-H-tetrazole (0.45M in acetonitrile, 56 mL, 25.3 mmol, solvent removed in vacuo prior to using) in tetrahydrofuran (100 mL) was added example 1, (4-{4-[({3-tert-butyl-1-[3-(hydroxymethyl)phenyl]-1H-pyrazol-5-yl}carbamoyl)amino]-3-fluorophenoxy}-N-methylpyridine-2-carboxamide, (5.00 g, 9.39 mmol) and di-t-butyl N,N-diethylphosphoramidite (2.11 g, 8.45 mmol). The reaction mixture was allowed to stir at room temperature for 2 h. The reaction mixture was then cooled to −40° C. and a slurry of m-chloroperoxybenzoic acid (85% in CH2Cl2, 2.74 g, 12.2 mmol) was added while keeping the reaction temperature below 0° C. The reaction mixture was allowed to warm to room temperature and stir for 10 min and then an aqueous.solution of NaHSO3 (10%, 40 mL) was added. After stirring for an additional 1 h at room temperature, the reaction was transferred to a separatory funnel and extracted with EtOAc. The organic layer was washed with NaHCO3 (2×50 mL), dried (NaSO4) and concentrated. The crude material was purified via column chromatography (CH2Cl2:2 M NH3 in MeOH, 98:2), followed by recrystallization (CH2Cl2/hexanes) to afford 3.57 g (52%) of the desired product as a white crystalline material. MS m/z 724.9 (M+H)+; Retention time (LC-MS): 3.74 min.

Workup

  1. customTo a room temperature solution of 1-H-tetrazole (0.45M in acetonitrile, 56 mL, 25.3 mmol, solvent removed in vacuo
  2. additionwas added example 1
  3. temperatureThe reaction mixture was then cooled to −40° C.
  4. customthe reaction temperature below 0° C
  5. temperatureto warm to room temperature
  6. stirringstir for 10 min
  7. stirringAfter stirring for an additional 1 h at room temperature
  8. customthe reaction was transferred to a separatory funnel
  9. extractionextracted with EtOAc
  10. washThe organic layer was washed with NaHCO3 (2×50 mL)
  11. dry with materialdried (NaSO4)
  12. concentrationconcentrated
  13. customThe crude material was purified via column chromatography (CH2Cl2:2 M NH3 in MeOH, 98:2)
  14. customfollowed by recrystallization (CH2Cl2/hexanes)

Sources & evidence

ORD record
ord-bd1215243d3943bd85e3fb6ae1591e3e
Source dataset
uspto-grants-2012_01
Patent number
US08101773B2

Reaction notes

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