Nitrogen → HCID 58466203, compound

HRID 335963Notes

Reaction equation

HRID 335963 reaction equation
Br[C:2]1[CH:15]=[C:14]([F:16])[C:13]2[O:12][C:11]3[C:6](=[CH:7][C:8]([O:17][CH3:18])=[CH:9][CH:10]=3)[C@@:5]3([CH2:22][O:21][C:20]([NH2:23])=[N:19]3)[C:4]=2[CH:3]=1.C([Li])CCC.N#N.[O:31]1[CH2:34][C:33](=[O:35])[CH2:32]1>C1COCC1>[NH2:23][C:20]1[O:21][CH2:22][C@:5]2([N:19]=1)[C:6]1[CH:7]=[C:8]([O:17][CH3:18])[CH:9]=[CH:10][C:11]=1[O:12][C:13]1[C:4]2=[CH:3][C:2]([C:33]2([OH:35])[CH2:34][O:31][CH2:32]2)=[CH:15][C:14]=1[F:16]

Participants

6

Reactant 4

HCID 947NitrogenHCID 150242543-OxetanoneHCID 58466212HCID 58466212, compoundHCID 178418339Butyllithium

Product 1

HCID 58466203HCID 58466203, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

To a RBF was added (S)-2′-bromo-4′-fluoro-7′-methoxy-5H-spiro[oxazole-4,9′-xanthen]-2-amine (2.17 g, 5.72 mmol, prepared as described in Method BB40 but using 4-bromo-2-fluorophenol and 2-bromo-5-methoxybenzoic acid) and THF (30 mL). The resulting mixture was then cooled to −78° C. and butyllithium solution, 2.5M in hexanes (8.01 mL, 20.03 mmol, Aldrich) was added drop wise under N2. The resulting mixture was then stirred at −78° C. for 15 min. Then, oxetan-3-one (1.031 g, 14.31 mmol, Molbridge LLC) in THF (3 mL) was added slowly. After addition, the mixture was stirred at −78° C. for 1.5 h under N2. Then, the mixture was quenched with saturated sodium bicarbonate solution (5 mL) at 0° C. and the mixture was extracted with EtOAc (2×30 mL). The combined organic extracts were dried over MgSO4 and concentrated. The residue was then dissolved in MeOH (30 mL) and silica gel was added. The solvent was removed and the solid mixture was purified by silica gel flash column chromatography using ISCO instrument (solid loading, 50%-100% EtOAc/hexane, then 10% MeOH in DCM) to give the title compound as a white solid. MS (ESI, positive ion) m/z: 373 (M+H).

Workup

  1. additionAfter addition
  2. stirringthe mixture was stirred at −78° C. for 1.5 h under N2
  3. customThen, the mixture was quenched with saturated sodium bicarbonate solution (5 mL) at 0° C.
  4. extractionthe mixture was extracted with EtOAc (2×30 mL)
  5. dry with materialThe combined organic extracts were dried over MgSO4
  6. concentrationconcentrated
  7. dissolutionThe residue was then dissolved in MeOH (30 mL)
  8. additionsilica gel was added
  9. customThe solvent was removed
  10. customthe solid mixture was purified by silica gel flash column chromatography

Sources & evidence

ORD record
ord-6a88a9ab8400443f8c60b2fb9e5f5549
Source dataset
uspto-grants-2014_11
Patent number
US08883782B2

Reaction notes

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