Methanol → HCID 11334587, compound

HRID 1071185Notes

Reaction equation

HRID 1071185 reaction equation
C(Cl)Cl.[C:4]([O:8][C:9]([NH:11][C:12]1[CH:13]=[C:14]2[C:19](=[CH:20][CH:21]=1)[O:18][C:17](=[O:22])[CH2:16][CH2:15]2)=[O:10])([CH3:7])([CH3:6])[CH3:5].[H-].C([Al+]CC(C)C)C(C)C.CO>O>[C:4]([O:8][C:9]([NH:11][C:12]1[CH:13]=[C:14]2[C:19](=[CH:20][CH:21]=1)[O:18][CH:17]([OH:22])[CH2:16][CH2:15]2)=[O:10])([CH3:7])([CH3:5])[CH3:6]

Participants

6

Reactant 4

HCID 887MethanolHCID 6344DichloromethaneHCID 10682957HCID 10682957, compoundHCID 21225700Diisobutylaluminumhydride

Product 1

HCID 11334587HCID 11334587, compound

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
-55 °C

Procedure

A 22-L three-neck round-bottom flask equipped with an overhead stirrer and an addition funnel was charged under nitrogen with 7 L of anhydrous methylene chloride and 800 g of 6-(tert-butyloxycarbonylamino)chroman-2-one (Example 1). The solution was cooled to about −55° C., and 2.66 L of diisobutylaluminum hydride (1.58 M solution in toluene, 4.2 mol) was slowly added through the addition funnel to the well-stirred solution. The addition rate was adjusted to keep the temperature of the reaction was between −50° C. and −65° C. requiring about 1.5 h overall. After an additional 1 h stirring, the reaction was complete by TLC. Methanol (870 mL) of was slowly added, keeping the temperature below −50° C. The reaction mixture was warmed up to about −20° C., and 790 g of Celite and 970 mL of water were added. The mixture was warmed to room temperature and stirred vigorously for 40 minutes. The mixture was filtered and the filter cake washed with 10.0 L of methylene chloride. The filtrate and the washings were combined and the solvent removed under reduced pressure at 50° C. The residue was transferred with 8.0 L of toluene into a 22-L three-neck round-bottom flask and dried azeotropically by distilling off 6 L of toluene under reduced pressure at 50° C. The volume of the remaining solution was adjusted to about 8 L with anhydrous toluene to provide a toluene solution of 6-(tert-butyloxycarbonylamino)chroman-2-ol.

Workup

  1. customA 22-L three-neck round-bottom flask equipped with an overhead stirrer and an addition funnel
  2. customwas between −50° C. and −65° C.
  3. customthe temperature below −50° C
  4. temperatureThe reaction mixture was warmed up to about −20° C.
  5. temperatureThe mixture was warmed to room temperature
  6. stirringstirred vigorously for 40 minutes
  7. filtrationThe mixture was filtered
  8. washthe filter cake washed with 10.0 L of methylene chloride
  9. customthe solvent removed under reduced pressure at 50° C
  10. customThe residue was transferred with 8.0 L of toluene into a 22-L three-neck round-bottom flask
  11. customdried azeotropically
  12. distillationby distilling off 6 L of toluene under reduced pressure at 50° C

Sources & evidence

ORD record
ord-647de40abc7b4ffcab6ca85183c705ca
Source dataset
uspto-grants-2005_06
Patent number
US06903227B2

Reaction notes

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