Diisobutylaluminumhydride → 9H-fluoren-9-ylmethyl 3-formyl-4-morpholinecarboxylate

HRID 1487030Notes

Reaction equation

HRID 1487030 reaction equation
[N:1]1([C:11]([O:13][CH2:14][CH:15]2[C:27]3[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=3[C:21]3[C:16]2=[CH:17][CH:18]=[CH:19][CH:20]=3)=[O:12])[CH2:6][CH2:5][O:4][CH2:3][CH:2]1[C:7](OC)=[O:8].[H-].C([Al+]CC(C)C)C(C)C>C1(C)C=CC=CC=1.ClCCl>[CH:7]([CH:2]1[CH2:3][O:4][CH2:5][CH2:6][N:1]1[C:11]([O:13][CH2:14][CH:15]1[C:16]2[CH:17]=[CH:18][CH:19]=[CH:20][C:21]=2[C:22]2[C:27]1=[CH:26][CH:25]=[CH:24][CH:23]=2)=[O:12])=[O:8]

Participants

5

Reactant 2

HCID 21225700DiisobutylaluminumhydrideHCID 733066324-(9H-fluoren-9-ylmethyl) 3-methyl 3,4-morpholinedicarboxylate

Product 1

HCID 898759159H-fluoren-9-ylmethyl 3-formyl-4-morpholinecarboxylate

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
-78 °C

Procedure

To a stirred solution of 4-(9H-fluoren-9-ylmethyl) 3-methyl 3,4-morpholinedicarboxylate (0.6 g, 1.633 mmol) in anhydrous toluene (80 mL) cooled to −78° C. in a dry-ice acetone bath under nitrogen was added dropwise 1.0 M diisobutylaluminium hydride in hexanes (6.53 mL, 6.53 mmol) over 4 minutes. The solution was stirred at −78° C. for 1.5 hours. The reaction was quenched at −78° C. with methanol (1.5 mL) and then aqueous HCl (1 M, 50 mL). The mixture was allowed to warm to ambient temperature and the phases separated. The aqueous was washed with ethyl acetate (2×50 mL). The combined organic extracts were dried (MgSO4), filtered and the solvent removed in vacuo to leave an oil. The residue was loaded in dichloromethane and purified by flash chromatography (Si) using 0-100% ethyl acetate-cyclohexane over 30 minutes. The appropriate fractions were combined and evaporated in vacuo to give the required product as a white foam, 329 mg. LCMS [LCMS4] Rt 2.43 min, m/z (ES+) 338 (M+H).

Workup

  1. customThe reaction was quenched at −78° C. with methanol (1.5 mL)
  2. temperatureto warm to ambient temperature
  3. customthe phases separated
  4. washThe aqueous was washed with ethyl acetate (2×50 mL)
  5. dry with materialThe combined organic extracts were dried (MgSO4)
  6. filtrationfiltered
  7. customthe solvent removed in vacuo
  8. customto leave an oil
  9. custompurified by flash chromatography (Si)
  10. customover 30 minutes
  11. customevaporated in vacuo

Sources & evidence

ORD record
ord-e7d3b85d6a5743ac8d016d6f8058501b
Source dataset
uspto-grants-2016_08
Patent number
US09428452B2

Reaction notes

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