Sodium borohydride → 4-((1R,2R,4R,5S,8S,12R)-2-hydroxy-4-methyl-6-oxo-9,13-dioxa-7-azatetracyclo[6.3.1.11,4.05,12]tridec-7-yl)-2-(trifluoromethyl)benzonitrile

HRID 563903Notes

Reaction equation

HRID 563903 reaction equation
[BH4-].[Na+].[CH3:3][C@:4]12[O:29][C@:7]3([C@@H:15]4[C@@H:11]([N:12]([C:17]5[CH:24]=[CH:23][C:20]([C:21]#[N:22])=[C:19]([C:25]([F:28])([F:27])[F:26])[CH:18]=5)[C:13](=[O:16])[C@H:14]14)[O:10][CH2:9][CH2:8]3)[C:6](=[O:30])[CH2:5]2>C1COCC1.CO>[OH:30][C@@H:6]1[CH2:5][C@@:4]2([CH3:3])[O:29][C@@:7]31[C@@H:15]1[C@@H:11]([N:12]([C:17]4[CH:24]=[CH:23][C:20]([C:21]#[N:22])=[C:19]([C:25]([F:26])([F:27])[F:28])[CH:18]=4)[C:13](=[O:16])[C@H:14]21)[O:10][CH2:9][CH2:8]3

Participants

5

Reactant 2

HCID 4311764Sodium borohydrideHCID 596360594-((1R,4R,5S,8S,12R)-4-methyl-2,6-dioxo-9,13-dioxa-7-azatetracyclo[6.3.1.11,4.05,12]tridec-7-yl)-2-(trifluoromethyl)benzonitrile

Product 1

HCID 596358654-((1R,2R,4R,5S,8S,12R)-2-hydroxy-4-methyl-6-oxo-9,13-dioxa-7-azatetracyclo[6.3.1.11,4.05,12]tridec-7-yl)-2-(trifluoromethyl)benzonitrileYield 99.5%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

Sodium borohydride (0.56 g, 14.7 mmol) was added in portions to a solution of Example 5 (2.9 g, 7.39 mmol) in THF (10 mL) and MeOH (10 mL) at 0° C. The reaction mixture was stirred for 15 min and quenched with drop-wise addition of aqueous saturated ammonium chloride (20 mL). The organic solvents were removed in vacuo and the residue was extracted with EtOAc. The organic layer was dried over anhydrous magnesium sulfate, filtered, and concentrated. The crude material was purified by silica gel chromatography using an 80 g ISCO column eluting with 0-100% EtOAc in CH2Cl2 at 70 mL/min. Concentration of appropriate fractions provided 2.9 g (99%) of Example 6 as a white solid.

Workup

  1. customquenched with drop-wise addition of aqueous saturated ammonium chloride (20 mL)
  2. customThe organic solvents were removed in vacuo
  3. extractionthe residue was extracted with EtOAc
  4. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe crude material was purified by silica gel chromatography
  8. washeluting with 0-100% EtOAc in CH2Cl2 at 70 mL/min

Sources & evidence

ORD record
ord-870aaf0e0ff04dbaa0ec30fed63f458c
Source dataset
uspto-grants-2011_11
Patent number
US08067582B2

Reaction notes

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