Sodium hydride → HCID 68508421, compound

HRID 1715322Notes

Reaction equation

HRID 1715322 reaction equation
[H-].[Na+].[CH:3]([NH:7][C:8]([CH:10]([O:20][C:21]1[CH:26]=[CH:25][C:24]([C:27]#[N:28])=[C:23]([C:29]([F:32])([F:31])[F:30])[CH:22]=1)[C:11]([CH3:19])([CH3:18])[CH2:12]OS(C)(=O)=O)=[O:9])([CH2:5][CH3:6])[CH3:4]>C1COCC1.CO>[C@@H:3]([N:7]1[CH2:19][C:11]([CH3:18])([CH3:12])[C@@H:10]([O:20][C:21]2[CH:26]=[CH:25][C:24]([C:27]#[N:28])=[C:23]([C:29]([F:31])([F:32])[F:30])[CH:22]=2)[C:8]1=[O:9])([CH2:5][CH3:6])[CH3:4]

Participants

5

Reactant 2

HCID 24758Sodium hydrideHCID 86608971HCID 86608971, compound

Product 1

HCID 68508421HCID 68508421, compound

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
22.5 °C

Procedure

Solid NaH (60 wt % dispersion in mineral oil, 16.6 g, 416 mmol) was added portion wise over 25 min to a cold (0-5° C.) sol'n of methanesulfonic acid 3-sec-butylcarbamoyl-3-(4-cyano-3-trifluoromethylphenoxy)-2,2-dimethylpropyl ester (104 g, 208 mmol) in 400 mL dry THF under an N2 atmosphere. The reaction mixture was allowed to warm to 20-25° C. and then stirred at this temp. for 90 h. The reaction mixture was quenched by adding it to 500 mL cold (5-10° C.) sat'd aq. NH4Cl. The phases were separated and the aqueous was extracted with ethyl acetate (“EtOAc”) (2×500 mL). The pale yellow organic was conc'd under vac (40-45° C.) to an orange-yellow oil/gum (83 g). The crude product was purified by extensive silica gel (230-400 mesh) column chromatography (EtOAc/Heptane) followed by crystallization (EtOAc/Heptane). The pure desired diastereomer was isolated as a white granular solid MS+: 355. m.p. 101-102° C. Optical rotation [α]58925=+180.10(in methanol) Elemental analysis results: Obsv'd (Theor.): C, 61.03 (61.01); H, 6.02 (5.97); N, 7.88 (7.91); F, 15.98 (16.08). HPLC analysis: Chiral purity: 100%.

Workup

  1. customThe reaction mixture was quenched
  2. additionby adding it to 500 mL cold (5-10° C.)
  3. customThe phases were separated
  4. extractionthe aqueous was extracted with ethyl acetate (“EtOAc”) (2×500 mL)
  5. customorganic was conc'd under vac (40-45° C.) to an orange-yellow oil/gum (83 g)
  6. customThe crude product was purified by extensive silica gel (230-400 mesh) column chromatography (EtOAc/Heptane)
  7. customfollowed by crystallization (EtOAc/Heptane)
  8. customThe pure desired diastereomer was isolated as a white granular solid MS+

Sources & evidence

ORD record
ord-9adc8bd1bc2b401b9fcb76f8abd62cb1
Source dataset
uspto-grants-2010_09
Patent number
US07799823B2

Reaction notes

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