Triphenylphosphine → HCID 86731239, compound

HRID 2277182Notes

Reaction equation

HRID 2277182 reaction equation
[CH:1]1([CH2:4][O:5][C:6]2[CH:11]=[CH:10][C:9]([C:12]3[O:13][C:14]4[C:20]([F:21])=[C:19]([OH:22])[CH:18]=[CH:17][C:15]=4[N:16]=3)=[CH:8][C:7]=2[F:23])[CH2:3][CH2:2]1.O[CH2:25][C@@H:26]([NH:28][C:29](=[O:35])OC(C)(C)C)[CH3:27].[C:36]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(C)C=CC=CC=1.N(C(OC(C)C)=O)=NC(OC(C)C)=O.Cl.C(OCC)(=O)C>C1COCC1>[CH:1]1([CH2:4][O:5][C:6]2[CH:11]=[CH:10][C:9]([C:12]3[O:13][C:14]4[C:20]([F:21])=[C:19]([O:22][CH2:25][C@@H:26]([NH:28][C:29](=[O:35])[CH3:36])[CH3:27])[CH:18]=[CH:17][C:15]=4[N:16]=3)=[CH:8][C:7]=2[F:23])[CH2:2][CH2:3]1

Participants

7

Reactant 5

HCID 11776TriphenylphosphineHCID 70231031,1-Dimethylethyl N-((1S)-2-hydroxy-1-methylethyl)carbamateHCID 21866389Hydrogen chloride-ethyl acetateHCID 66880968DIAD tolueneHCID 86731237HCID 86731237, compound

Product 1

HCID 86731239HCID 86731239, compoundYield 53.9%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 2-(4-(cyclopropylmethoxy)-3-fluorophenyl)-7-fluoro-1,3-benzoxazol-6-ol (3.96 g), tert-butyl ((2S)-1-hydroxypropan-2-yl)carbamate (3.28 g) and triphenylphosphine (4.91 g) in THF (50 mL) was added dropwise diisopropyl azodicarboxylate toluene solution (1.9 M, 9.85 mL) at 0° C., and the mixture was stirred at room temperature for 30 min. The reaction mixture was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (NH, hexane/ethyl acetate) to give a solid. To this solid was added 4 M hydrogen chloride/ethyl acetate (50 mL), and the mixture was stirred at room temperature for 10 min, and concentrated. To the residue were added pyridine (50 mL) and acetic anhydride (50 mL), and the mixture was stirred at room temperature for 15 min. The reaction mixture was concentrated under reduced pressure, and the obtained solid was dissolved in ethyl acetate/methanol, and the solution was subjected to silica gel column chromatography (NH, ethyl acetate), and concentrated. The obtained solid was recrystallized (hexane/ethyl acetate) to give the title compound as white crystals (2.80 g).

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. customthe residue was purified by silica gel column chromatography (NH, hexane/ethyl acetate)
  3. customto give a solid
  4. stirringthe mixture was stirred at room temperature for 10 min
  5. concentrationconcentrated
  6. additionTo the residue were added pyridine (50 mL) and acetic anhydride (50 mL)
  7. stirringthe mixture was stirred at room temperature for 15 min
  8. concentrationThe reaction mixture was concentrated under reduced pressure
  9. dissolutionthe obtained solid was dissolved in ethyl acetate/methanol
  10. concentrationconcentrated
  11. customThe obtained solid was recrystallized (hexane/ethyl acetate)

Sources & evidence

ORD record
ord-4a6e170bef584ad8b7b294d64156625a
Source dataset
uspto-grants-2015_09
Patent number
US09133129B2

Reaction notes

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