N-methyl-2-pyrrolidone → HCID 59201687, compound

HRID 451753Notes

Reaction equation

HRID 451753 reaction equation
[O:1]=[C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[C:4](=[O:11])[N:3]1[CH2:12][CH:13]=[O:14].CN1CCC[C:17]1=[O:21].[CH:22]1(C=O)[CH2:27][CH2:26][CH2:25][CH2:24][CH2:23]1.N1CCC[C@H]1C(O)=O>O>[CH:22]1([C@H:13]([OH:14])[C@H:12]([N:3]2[C:4](=[O:11])[C:5]3[C:10](=[CH:9][CH:8]=[CH:7][CH:6]=3)[C:2]2=[O:1])[CH:17]=[O:21])[CH2:27][CH2:26][CH2:25][CH2:24][CH2:23]1

Participants

6

Reactant 4

HCID 13387N-methyl-2-pyrrolidoneHCID 16275CyclohexanecarboxaldehydeHCID 76201Phthalylglycine aldehydeHCID 145742L-Proline

Product 1

HCID 59201687HCID 59201687, compound

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

2-(1,3-dioxoisoindolin-2-yl)acetaldehyde (2.04 g, 10.7 mmol) was dissolved into a minimal amount of anhydrous N-methylpyrrolidinone (5.0 mL). Heating was required for full dissolution. The solution was cooled to rt and cyclohexanecarboxaldehyde (5.60 g, 50 mmol) was added. The solution was cooled to 0° C. and solid L-proline (0.40 g, 3.4 mmol) was added in one portion. The reaction was stirred for 1 h at 0° C. and the orange mixture was stored in the refrigerator (6° C.) for 36 h. The crude reaction was taken up in 5:1 Et2O/Hexanes (100 mL) and water (20 mL). The layers were separated and the aqueous phase mixture was extracted with 5:1 Et2O/Hexanes (3×10 mL). The combined organic layers were washed with water (5×10 mL) and brine (3×10 mL), dried over Na2SO4, decanted and stripped to give crude (2S,3S)-3-cyclohexyl-2-(1,3-dioxoisoindolin-2-yl)-3-hydroxypropanal (4.55 g), which was used in the next step without purification.

Workup

  1. temperatureHeating
  2. dissolutionwas required for full dissolution
  3. temperatureThe solution was cooled to 0° C.
  4. waitthe orange mixture was stored in the refrigerator (6° C.) for 36 h
  5. customThe crude reaction
  6. customThe layers were separated
  7. extractionthe aqueous phase mixture was extracted with 5:1 Et2O/Hexanes (3×10 mL)
  8. washThe combined organic layers were washed with water (5×10 mL) and brine (3×10 mL)
  9. dry with materialdried over Na2SO4
  10. customdecanted

Sources & evidence

ORD record
ord-c59ed84105be49859b8d855038425ade
Source dataset
uspto-grants-2013_07
Patent number
US08487108B2

Reaction notes

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