Lithium borohydride → HCID 86299123, compound

HRID 589048Notes

Reaction equation

HRID 589048 reaction equation
[BH4-].[Li+].[CH3:3][C:4]1[C:8]([C:9]2[C:18]3[O:17][CH:16]([C:19](OCC)=[O:20])[CH:15]([C:24]4[CH:29]=[CH:28][CH:27]=[CH:26][N:25]=4)[N:14]4[C:30](=[O:32])[NH:31][C:12]([C:13]=34)=[CH:11][CH:10]=2)=[C:7]([CH3:33])[O:6][N:5]=1>O1CCCC1>[CH3:3][C:4]1[C:8]([C:9]2[C:18]3[O:17][CH:16]([CH2:19][OH:20])[CH:15]([C:24]4[CH:29]=[CH:28][CH:27]=[CH:26][N:25]=4)[N:14]4[C:30](=[O:32])[NH:31][C:12]([C:13]=34)=[CH:11][CH:10]=2)=[C:7]([CH3:33])[O:6][N:5]=1

Participants

4

Reactant 2

HCID 4148881Lithium borohydrideHCID 90409776HCID 90409776, compound

Product 1

HCID 86299123HCID 86299123, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
70 °C

Procedure

Lithium tetrahydroborate (1.6 mg, 0.071 mmol) was added to ethyl 7-(3,5-dimethylisoxazol-4-yl)-2-oxo-4-pyridin-2-yl-1,2,4,5-tetrahydroimidazo[1,5,4-de][1,4]benzoxazine-5-carboxylate (20 mg, 0.05 mmol), from Example 20, in tetrahydrofuran (3 mL). The reaction was stirred at 70° C. for 3 h, then partitioned between water and ethyl acetate. The organic layer was concentrated and the crude product was purified by FCC on silica gel eluting a hexane:ethyl acetate gradient to obtain the product as a mixture of diastereomers. The isomers were separated by prep chiral column chromatography using the following conditions: Column: phenomenex Lux Cellulose C-2 5 μm, 21, 2×250 mm, Mobile phase: 45% EtOH/Hexanes, Gradient condition: isocratic at 18 mL/min, Loading: 13.5 mg in 900 μL, run time: 18 min, peak time: 9.0, 12.1, 24.2 and 15.0 min.

Workup

  1. custompartitioned between water and ethyl acetate
  2. concentrationThe organic layer was concentrated
  3. customthe crude product was purified by FCC on silica gel eluting a hexane
  4. customethyl acetate gradient to obtain the product
  5. additionas a mixture of diastereomers
  6. customThe isomers were separated by prep chiral column chromatography
  7. custom18 min, peak time
  8. custom9.0, 12.1, 24.2 and 15.0 min.

Sources & evidence

ORD record
ord-39318e413fa94f9cb1c7076811879ff7
Source dataset
uspto-grants-2016_01
Patent number
US09227985B2

Reaction notes

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