Triphenylphosphine → HCID 86682291, compound

HRID 529728Notes

Reaction equation

HRID 529728 reaction equation
[N:1]([CH2:4][C@H:5]([C:10]1[CH:15]=[CH:14][C:13]([O:16][CH3:17])=[C:12]([Br:18])[CH:11]=1)[C:6]([CH3:9])([OH:8])[CH3:7])=[N+]=[N-].C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.CCN(C(C)C)C(C)C.C1N=CN([C:52](N2C=NC=C2)=[O:53])C=1>[NH4+].[Cl-].C1COCC1.O>[Br:18][C:12]1[CH:11]=[C:10]([C@@H:5]2[C:6]([CH3:9])([CH3:7])[O:8][C:52](=[O:53])[NH:1][CH2:4]2)[CH:15]=[CH:14][C:13]=1[O:16][CH3:17]

Participants

8

Reactant 4

HCID 11776TriphenylphosphineHCID 682631,1'-CarbonyldiimidazoleHCID 81531DiisopropylethylamineHCID 86682294HCID 86682294, compound

Product 1

HCID 86682291HCID 86682291, compoundYield 79.6%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×HCID 25517Ammonium ChlorideSolvent

Conditions

Temperature
60 °C

Procedure

To a 25 mL round bottom flask containing (S)-4-azido-3-(3-bromo-4-methoxyphenyl)-2-methylbutan-2-ol (38 mg, 0.12 mmol) were added PPh3 (48 mg, 0.18 mmol), THF (2 mL) and water (0.2 mL). The resulting reaction mixture was heated to reflux for 2 hrs. Volatiles were removed under vacuum. To the residue was added 2 mL THF, DIEA (0.063 mL, 0.36 mmol) and CDI (39 mg, 0.24 mmol). The resulting reaction mixture was heated at 60° C. for 3 hrs. It was then diluted with 10 mL saturated NH4Cl and extracted with 15 mL EtOAc. The organics were dried over sodium sulfate, filtered and concentrated. Crude product was purified on a Combiflash prepacked silica gel column which was eluted with EtOAc to give 30 mg of the desired product (intermediate N). 1H NMR (500 MHz, CDCl3): δ 7.41 (s, 1H), 7.16 (d, J=7.8 Hz, 1H), 6.88 (d, J=8.5 Hz, 1H), 6.76 (s, 1H), 3.90 (s, 3H), 3.65 (t, J=11.4 Hz, 1H), 3.46 (br, 1H), 3.0 (br, 1H), 1.34 (s, 3H), 1.32 (s, 3H).

Workup

  1. customThe resulting reaction mixture
  2. temperaturewas heated
  3. temperatureto reflux for 2 hrs
  4. customVolatiles were removed under vacuum
  5. customThe resulting reaction mixture
  6. extractionextracted with 15 mL EtOAc
  7. dry with materialThe organics were dried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customCrude product was purified on a Combiflash prepacked silica gel column which
  11. washwas eluted with EtOAc

Sources & evidence

ORD record
ord-784f167e785f4712a396bb6ba4861a49
Source dataset
uspto-grants-2016_05
Patent number
US09346825B2

Reaction notes

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