Methanol → HCID 90412642, compound

HRID 1746635Notes

Reaction equation

HRID 1746635 reaction equation
CO.[I:3][C:4]1[C:5](=[O:35])[C@@H:6]2[O:10][C:9]([CH3:12])([CH3:11])[O:8][C@@H:7]2[C:13]=1[CH2:14][O:15][C:16]([C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1)([C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1)[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1.[BH4-].[Na+]>[Cl-].[Na+].O>[I:3][C:4]1[C@H:5]([OH:35])[C@@H:6]2[O:10][C:9]([CH3:12])([CH3:11])[O:8][C@@H:7]2[C:13]=1[CH2:14][O:15][C:16]([C:23]1[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=1)([C:17]1[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=1)[C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1

Participants

5

Reactant 3

HCID 887MethanolHCID 4311764Sodium borohydrideHCID 90412698HCID 90412698, compound

Product 1

HCID 90412642HCID 90412642, compound

Reagents, catalysts & solvents 1

HCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
-10 °C

Procedure

Into a 500 L reactor was charged 100 L of methanol, followed by addition of 6 (9.7 kg) and CeCl3-7H2O (7.2 kg) in 1 kg portions over 0.5 hour. Temperature of the reaction mixture rose ˜5° C. during the addition. The reaction mixture was cooled down to −10° C., and NaBH4 (0.77 kg) was added in portions (˜150 g) over 1 hour resulting in strong H2 evolution with elevation of the reaction temperature. The transparent reaction mixture was then stirred for 2 hours at 0° C. until HPLC indicated complete conversion. Then 150 L of brine were added to result in white precipitates. The suspension was concentrated under vacuum to remove most of methanol and ethyl acetate (100 L) was added to the resulting residue and the mixture was stirred for 30 minutes. Then the organic layer was separated washed with brine (20 L) and dried over sodium sulfate, filtered and concentrated to dryness, and the residue was used directly in the next step. Sample from the reaction mixture and standard samples for compounds 6 and 7 were applied to a commercial silica gel TLC plate, with petroleum ether/ethyl acetate=4:1 as the mobile phase. 6 and 7 can be detected under UV254 or visualized using iodine treatment. The Rf for 6 was ˜0.55 while the Rf for compound 7 was ˜0.57; 1H-NMR (300 MHz, CDCl3) δ 7.21-7.48 (m, 15H), 5.20 (d, J=5.7 Hz, 1H), 4.77 (t, J=5.7 Hz, 1H), 4.39 (dd, J=5.4, 11.2 Hz, 1H), 3.90 (d, J=12.0 Hz, 1H), 3.79 (d, J=12.0 Hz, 1H), 2.81 (d, J=11.2 Hz, 1H), 1.43 (s, 3H), 1.32 (s, 3H); 13C-NMR DEPT-135 (75 MHz, CDCl3) δ 128.79, 127.89, 127.11, 82.91, 78.14, 76.48, 62.58 (OCH2—), 27.54, 27.11.

Workup

  1. additionTemperature of the reaction mixture rose ˜5° C. during the addition
  2. customresulting in strong H2 evolution with elevation of the reaction temperature
  3. customto result in white precipitates
  4. concentrationThe suspension was concentrated under vacuum
  5. customto remove most of methanol and ethyl acetate (100 L)
  6. additionwas added to the resulting residue
  7. stirringthe mixture was stirred for 30 minutes
  8. customThen the organic layer was separated
  9. washwashed with brine (20 L)
  10. dry with materialdried over sodium sulfate
  11. filtrationfiltered
  12. concentrationconcentrated to dryness

Sources & evidence

ORD record
ord-ffa384e7d6d44de4b2dcf070da1fb536
Source dataset
uspto-grants-2015_10
Patent number
US09150520B2

Reaction notes

Loading…