Triphenylphosphine → HCID 178457566, compound

HRID 2222434Notes

Reaction equation

HRID 2222434 reaction equation
[CH3:1][C:2]([CH3:28])([CH2:4][NH:5][C:6]([CH2:8][C@@H:9]1[CH2:27][CH2:26][C@@:12]2([O:16][C@:15]3([CH:21]4[CH2:22][CH:23]5[CH2:25][CH:19]([CH2:20]4)[CH2:18][CH:17]3[CH2:24]5)[O:14][O:13]2)[CH2:11][CH2:10]1)=[O:7])[NH2:3].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C[Si](N=[N+]=[N-])(C)C.N(C(OC(C)C)=O)=NC(OC(C)C)=O>C1COCC1.O>[CH3:1][C:2]([CH3:28])([CH2:4][NH:5][C:6]([CH2:8][C@@H:9]1[CH2:27][CH2:26][C@:12]2([O:16][C:15]3([CH:21]4[CH2:20][CH:19]5[CH2:25][CH:23]([CH2:22]4)[CH2:24][CH:17]3[CH2:18]5)[O:14][O:13]2)[CH2:11][CH2:10]1)=[O:7])[NH2:3]

Participants

7

Reactant 4

HCID 11776TriphenylphosphineHCID 75555Diisopropyl diazene-1,2-dicarboxylateHCID 78378AzidotrimethylsilaneHCID 178457567HCID 178457567, compound

Product 1

HCID 178457566HCID 178457566, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a mixture of OZ277 free base (0.46 g, 1.17 mmol), triphenylphosphine (0.77 g, 2.94 mmol), and trimethylsilyl azide (0.34 g, 2.95 mmol) in THF (20 ml) at 0° C. under N2 was added dropwise diisopropyl azodicarboxylate (0.71 g, 3.51 mmol). The mixture was slowly warmed to rt and stirred for 72 h. The reaction mixture was diluted with water (50 ml) and extracted with EtOAc (2×50 ml). The combined extracts were washed with saturated aqueous NaHCO3 (2×50 ml) and brine (50 ml), dried over MgSO4, filtered, and concentrated. To a solution of the residue CHCl3 (20 ml) was added a solution of p-toluenesulfonic acid monohydrate (0.22 g) in ethanol (10 ml). After evaporation of the solvents, the crude product was purified by crystallization from MeOH/CH2Cl2 (1:4) to afford trioxolane OZ373 (0.12 g, 17%) as a colorless solid. mp 220° C. dec; 1H NMR (500 MHz, CD3OD) δ1.28-1.38 (m, 2H), 1.38 (s, 6H), 1.65-2.09 (m, 21H), 2.37 (s, 3H), 2.86 (d, J=6.8 Hz, 2H), 4.58 (s, 2H), 7.23 (d, J=7.8 Hz, 2H), 7.70 (d, J=7.8 Hz, 2H); 13C NMR (125.7 MHz, CD3OD) δ21.30, 23.79, 27.97, 28.37, 30.04, 30.87, 34.87, 35.77, 35.78, 36.04, 37.80, 37.88, 54.02, 55.39, 109.53, 112.40, 126.97, 129.81, 141.66, 157.09.

Workup

  1. extractionextracted with EtOAc (2×50 ml)
  2. washThe combined extracts were washed with saturated aqueous NaHCO3 (2×50 ml) and brine (50 ml)
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. additionTo a solution of the residue CHCl3 (20 ml) was added a solution of p-toluenesulfonic acid monohydrate (0.22 g) in ethanol (10 ml)
  7. customAfter evaporation of the solvents
  8. customthe crude product was purified by crystallization from MeOH/CH2Cl2 (1:4)

Sources & evidence

ORD record
ord-6e76b9ce0bf64ba4abab6311c802dc20
Source dataset
uspto-grants-2008_05
Patent number
US07371778B2

Reaction notes

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