Hydrochloric Acid → HCID 10110107, compound

HRID 2306084Notes

Reaction equation

HRID 2306084 reaction equation
[Li+].[CH2:2]([O:9][NH:10][C@@H:11]([CH2:16][O:17][C:18]1[CH:23]=[CH:22][C:21]([Br:24])=[CH:20][CH:19]=1)[CH2:12]C([O-])=O)[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.C1C=CC(P(N=[N+]=[N-])(C2C=CC=CC=2)=[O:32])=CC=1.C([N:45]([CH:48](C)C)CC)(C)C.Cl.[Na+].[Cl-]>C1COCC1>[CH2:2]([O:9][N:10]1[C@@H:11]([CH2:16][O:17][C:18]2[CH:19]=[CH:20][C:21]([Br:24])=[CH:22][CH:23]=2)[CH2:12][NH:45][C:48]1=[O:32])[C:3]1[CH:4]=[CH:5][CH:6]=[CH:7][CH:8]=1

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 5234Sodium ChlorideHCID 81531DiisopropylethylamineHCID 199401P,P-Diphenylphosphinic azideHCID 88171941HCID 88171941, compound

Product 1

HCID 10110107HCID 10110107, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
30 °C

Procedure

A suspension of Example 3E in THF (2.1 L) was treated with DPPA (90.5 g) and diisopropylethyl amine (56 mL), heated to reflux, stirred for 3 hours, cooled to 30° C., poured into ice cold 10% HCl, and stirred vigorously. The organic phase was treated with 10% HCl (500 mL) and NaCl (75 g). The aqueous phase was separated and washed with ethyl acetate. The extract was washed sequentially with water, saturated NaHCO3, and brine and concentrated. The concentrate was treated with toluene (550 mL), warmed to reflux, cooled to 35° C., treated with heptane (800 mL) over 2 hours, and filtered. The solid was dissolved in 1:1 THF/toluene (700 mL), and the resulting solution was washed with saturated NaHCO3 and brine, and concentrated. The solid was dried under vacuum (100 mm Hg) at 50° C. with a nitrogen bleed to provide 54.6 g of the desired product. 1H NMR (300 MHz, CDCl3) δ7.45 (m, 2H) 7.35 (m, 5H), 6.58 (m, 2H), 5.35 (br s, 1H), 5.05 (d, 1H, J=11 Hz), 4.94 (d, 1H, J=11 Hz), 3.85 (m, 1H), 3.73 (dd, 1H, J=7, 9 Hz), 3.55 (dd, 1H, J=7, 9 Hz), 3.51 (t, 1H, J=8 Hz), 3.25 (t, 1H, J=9 Hz).

Workup

  1. temperatureheated
  2. temperatureto reflux
  3. stirringstirred vigorously
  4. customThe aqueous phase was separated
  5. washwashed with ethyl acetate
  6. washThe extract was washed sequentially with water, saturated NaHCO3, and brine
  7. concentrationconcentrated
  8. additionThe concentrate was treated with toluene (550 mL)
  9. temperaturewarmed
  10. temperatureto reflux
  11. temperaturecooled to 35° C.
  12. additiontreated with heptane (800 mL) over 2 hours
  13. filtrationfiltered
  14. dissolutionThe solid was dissolved in 1:1 THF/toluene (700 mL)
  15. washthe resulting solution was washed with saturated NaHCO3 and brine
  16. concentrationconcentrated
  17. customThe solid was dried under vacuum (100 mm Hg) at 50° C. with a nitrogen

Sources & evidence

ORD record
ord-b270bd9e67d34089849d3ecd9bfcf780
Source dataset
uspto-grants-2002_08
Patent number
US06441189B1

Reaction notes

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