Water → HCID 14525802, compound

HRID 451353Notes

Reaction equation

HRID 451353 reaction equation
FC(F)(F)S([O:6][C@@H:7]1[C@@H:12]([O:13][CH2:14][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[C@H:11]([O:21][CH2:22][C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[C@H:10]([O:29][CH2:30][C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=2)[O:9][CH2:8]1)(=O)=O.N([O-])=O.[Na+].O>CN(C=O)C>[CH2:14]([O:13][C@H:12]1[C@H:11]([O:21][CH2:22][C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[C@H:10]([O:29][CH2:30][C:31]2[CH:32]=[CH:33][CH:34]=[CH:35][CH:36]=2)[O:9][CH2:8][C@@H:7]1[OH:6])[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1

Participants

5

Reactant 3

HCID 962WaterHCID 23668193Sodium NitriteHCID 59378767HCID 59378767, compound

Product 1

HCID 14525802HCID 14525802, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
10 °C

Procedure

The triflate (12) was dissolved in DMF (36.2 kg, 3.02 kg/kg starting material) and cooled to 10° C. Sodium nitrite (5.9 kg, 3.0 equivalents) was added, the solution exothermed to approximately 30° C., then the reaction mixture was cooled to 15° C. to 25° C. and stirred for 12-16 h. The mixture was cooled to 5° C., and water (152 kg, 4.2 kg/kg DMF) was added at a rate that kept the temperature <15° C. The resulting mixture was agitated at 10° C. for 2 hours. The solids were filtered and washed with water (2×12 kg). The filtered solids were dissolved in ethyl acetate (21.6 kg, 1.8 kg/kg starting material). The solution was washed with brine (15.5 kg), dried with MgSO4 (2.5 kg), filtered, and the filtrate was concentrated to dryness under vacuum at 35° C. Isopropanol (9.5 kg) was added and heated to 75° C. to dissolve the crude product. Heptane (24.6 kg) was added to the solution and the mixture cooled to 15° C. to 25° C. The mixture was further cooled to 0° C. and stirred overnight. The solids were filtered and washed with heptane (2×8.2 kg). The material was dried in a vacuum oven. (3S,4R,5S,6R)-4,5,6-Tris(benzyloxy)tetrahydro-2H-pyran-3-ol (13) was obtained as a yellow solid, 5.3 kg (44%). 1H NMR (300 MHz, CDCl3): δ 7.37 (m, 15H), 4.96 (d, J=11 Hz, 1H), 4.80 (m, 2H), 4.68 (d, J=12 Hz, 1H), 4.61 (m, 2H), 4.53 (d, J=12 Hz, 1H), 3.78 (m, 1H), 3.67 (m, 3H), 3.50 (dd, J=9, 3 Hz, 1H), 2.42 (br s, 1H).

Workup

  1. customexothermed to approximately 30° C.
  2. temperaturethe reaction mixture was cooled to 15° C. to 25° C.
  3. temperatureThe mixture was cooled to 5° C.
  4. customthe temperature <15° C
  5. stirringThe resulting mixture was agitated at 10° C. for 2 hours
  6. filtrationThe solids were filtered
  7. washwashed with water (2×12 kg)
  8. dissolutionThe filtered solids were dissolved in ethyl acetate (21.6 kg, 1.8 kg/kg starting material)
  9. washThe solution was washed with brine (15.5 kg)
  10. dry with materialdried with MgSO4 (2.5 kg)
  11. filtrationfiltered
  12. concentrationthe filtrate was concentrated to dryness under vacuum at 35° C
  13. additionIsopropanol (9.5 kg) was added
  14. temperatureheated to 75° C.
  15. dissolutionto dissolve the crude product
  16. additionHeptane (24.6 kg) was added to the solution
  17. temperaturethe mixture cooled to 15° C. to 25° C
  18. temperatureThe mixture was further cooled to 0° C.
  19. stirringstirred overnight
  20. filtrationThe solids were filtered
  21. washwashed with heptane (2×8.2 kg)
  22. customThe material was dried in a vacuum oven

Sources & evidence

ORD record
ord-459b22e82b8f4decbddb6d75a4854f6b
Source dataset
uspto-grants-2013_07
Patent number
US08487110B2

Reaction notes

Loading…