Dichloromethane → HCID 118511179, compound

HRID 1478197Notes

Reaction equation

HRID 1478197 reaction equation
[CH:1]1([N:7]2[C:11](=[O:12])[C:10]([NH:13][C:14]([C:16]3[C:20]([CH3:21])=[C:19]([C@H:22]([O:26][CH2:27][C:28]([CH3:30])=[CH2:29])[C@@H:23]([OH:25])[CH3:24])[O:18][N:17]=3)=[O:15])=[C:9]([CH3:31])[N:8]2[CH3:32])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.C(B(CC)CC)C.[BH4-].[Na+].C(Cl)Cl>C1COCC1>[CH:1]1([N:7]2[C:11](=[O:12])[C:10]([NH:13][C:14]([C:16]3[C:20]([CH3:21])=[C:19]([C@H:22]4[C@H:23]([CH3:24])[O:25][C:28]([CH3:30])([CH3:29])[CH2:27][O:26]4)[O:18][N:17]=3)=[O:15])=[C:9]([CH3:31])[N:8]2[CH3:32])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

6

Reactant 4

HCID 6344DichloromethaneHCID 7357TriethylboraneHCID 4311764Sodium borohydrideHCID 118511025HCID 118511025, compound

Product 1

HCID 118511179HCID 118511179, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Mercuric trifluoroacetate (3.92 g, 9.19 mmol) was added portionwise to N-(2-cyclohexyl-1,5-dimethyl-3-oxo-2,3-dihydro-1H-pyrazol-4-yl)-5-((1R,2S)-2-hydroxy-1-((2-methylallyl)oxy)propyl)-4-methylisoxazole-3-carboxamide (3.59 g, 8.03 mmol) in THF (160 mL) at room temperature. Mercuric oxide red (1.99 g, 9.19 mmol) was added and the resulting reaction mixture was stirred at room temperature. After 1 h the reaction was cooled to −78° C. and triethylborane (16.84 ml, 16.84 mmol) was added dropwise followed by sodium borohydride (579 mg, 15.31 mmol) portionwise. After 1 h at −78° C. the reaction was allowed to warm gradually to room temperature. The resulting mixture was quenched by the addition of brine and EtOAc, separated, dried over Na2SO4 and concentrated under reduced pressure. DCM (200 ml) and Biotage Si-Thiol (17 g, 1.4 mmol/g load, ˜3 eq) were added and the resulting suspension was stirred at room temperature for 18 h. The reaction was filtered, washed with DCM and concentrated under reduced pressure. The crude material was adsorbed onto silica and purification by chromatography eluting with 90-95% EtOAc in iso-hexane afforded the title compound (>95% ee);

Workup

  1. customthe resulting reaction mixture
  2. temperatureAfter 1 h the reaction was cooled to −78° C.
  3. temperatureto warm gradually to room temperature
  4. customThe resulting mixture was quenched by the addition of brine and EtOAc
  5. customseparated
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated under reduced pressure
  8. stirringthe resulting suspension was stirred at room temperature for 18 h
  9. filtrationThe reaction was filtered
  10. washwashed with DCM
  11. concentrationconcentrated under reduced pressure
  12. customThe crude material was adsorbed onto silica and purification by chromatography
  13. washeluting with 90-95% EtOAc in iso-hexane

Sources & evidence

ORD record
ord-3cba58d190ac4418843f0076feb67db8
Source dataset
uspto-grants-2016_08
Patent number
US09403810B2

Reaction notes

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