Boron trifluoride etherate → HCID 123843496, compound

HRID 1509133Notes

Reaction equation

HRID 1509133 reaction equation
[C:1]([O:5][C:6](=[O:35])[NH:7][C:8]1([C:12]2[CH:17]=[CH:16][C:15]([C:18]3[C:19]([C:29]4[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=4)=[CH:20][C:21]4[NH:26][C:25](=O)[CH2:24][O:23][C:22]=4[N:28]=3)=[CH:14][CH:13]=2)[CH2:11][CH2:10][CH2:9]1)([CH3:4])([CH3:3])[CH3:2].B(F)(F)F.CCOCC.[BH4-].[Na+].C([O-])(O)=O.[Na+]>C1COCC1.CCOC(C)=O>[C:1]([O:5][C:6](=[O:35])[NH:7][C:8]1([C:12]2[CH:13]=[CH:14][C:15]([C:18]3[C:19]([C:29]4[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=4)=[CH:20][C:21]4[NH:26][CH2:25][CH2:24][O:23][C:22]=4[N:28]=3)=[CH:16][CH:17]=2)[CH2:11][CH2:10][CH2:9]1)([CH3:4])([CH3:2])[CH3:3]

Participants

7

Reactant 4

HCID 8000Boron trifluoride etherateHCID 516892Sodium BicarbonateHCID 4311764Sodium borohydrideHCID 67256382HCID 67256382, compound

Product 1

HCID 123843496HCID 123843496, compoundYield 48%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of tert-butyl(1-(4-(2-oxo-7-phenyl-2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazin-6-yl)phenyl)cyclobutyl)carbamate (143 mg, 0.42 mmol) in dry THF (4 mL) was added boron trifluoride diethyl etherate (91 μL, 0.73 mmol) and sodium borohydride (27 mg, 0.73 mmol) at 0° C. under nitrogen. The resulting mixture was stirred for 4 h at 0° C. AcOEt (5 mL) and a saturated solution of NaHCO3 (10 mL) were added. The aqueous phase was extracted with dichloromethane (3×) using a phase separator (Isolute® SPE). The combined organic phases were concentrated to dryness under reduced pressure. The resulting residue was purified by Biotage silica gel chromatography (gradient 0 to 2% MeOH in DCM) to give the title compound as a white solid (66 mg, 48%). 1H NMR (500 MHz, CDCl3): 7.21-7.26 (7H, m), 7.14-7.12 (2H,m), 6.97 (1H, s), 4.48 (2H, t), 3.48 (2H, br s),2.55-2.25 (4H, m), 2.06-1.98 (1H, m), 1.82-1.73 (1H, m), 1.44-1.15 (9H, br).

Workup

  1. extractionThe aqueous phase was extracted with dichloromethane (3×)
  2. concentrationThe combined organic phases were concentrated to dryness under reduced pressure
  3. customThe resulting residue was purified by Biotage silica gel chromatography (gradient 0 to 2% MeOH in DCM)

Sources & evidence

ORD record
ord-0de78d46f3084951becf63aef6f6048d
Source dataset
uspto-grants-2015_12
Patent number
US09221838B2

Reaction notes

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