Acetone → HCID 71294533, compound

HRID 340814Notes

Reaction equation

HRID 340814 reaction equation
CC(C)=O.[CH2:5]([O:7][C:8](=[O:34])[C@@H:9]1[CH2:13][C@@H:12]([OH:14])[CH2:11][N:10]1[C:15]([C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1)([C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)[CH3:6].C(N(CC)CC)C.O>C(Cl)Cl>[CH2:5]([O:7][C:8](=[O:34])[C@@H:9]1[CH2:13][C:12](=[O:14])[CH2:11][N:10]1[C:15]([C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1)([C:16]1[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=1)[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)[CH3:6]

Participants

6

Reactant 4

HCID 180AcetoneHCID 962WaterHCID 8471TriethylamineHCID 71294608HCID 71294608, compound

Product 1

HCID 71294533HCID 71294533, compoundYield 75%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Procedure

To a 100 mL round bottom flask containing 20 mL CH2Cl2 was added 0.54 mL (6.20 mmol; 1.2 eq) of COCl2 in 2 mL CH2Cl2. The flask was then chilled to −60° C. (acetone bath and cold finger) under argon balloon. To this was added 0.88 mL dry (molecular civ treated) DMSO in 1 mL dry (MgSO4 treated) CH2Cl2 drop wise. The mixture was allowed to stir for 15 min. before being brought up to −30° C. where 2.02 g (6.17 mmol) of N-trityl-trans-4-hydroxy-L-proline ethyl ester in 4 mL CH2Cl2 was added dropwise over 10 min. The resulting solution was allowed to stir for 1 h at −30° C. under argon balloon. To complete the reaction, 3.6 mL (>5 eq) of triethylamine was slowly added. The flask was then allowed to warm to room temperature where 100 mL of water was added. The mixture was then extracted with Et2O (3×100 mL). The organic extracts were combined, dried with Na2SO4 and concentrated via rotovap to a solid crude. The remaining crude was then immediately separated by silica gel (90% hexanes, 9% ethylacetate, 1% TEA, Rf=0.2). The fractions containing the product were combined, concentrated, and placed on a high vacuum pump leaving 1.51 g of N-trityl-4-keto-L-proline ethyl ester, as a white foam, a yield of 75%. This product, once isolated, was then used within 4-6 h in the addition step (trityl group readily decomposes) without further purification.

Workup

  1. additionTo this was added 0.88 mL
  2. dry with materialdry (molecular civ treated) DMSO in 1 mL
  3. dry with materialdry (MgSO4 treated) CH2Cl2
  4. custombefore being brought up to −30° C.
  5. additionwas added dropwise over 10 min
  6. stirringto stir for 1 h at −30° C. under argon balloon
  7. additionwas slowly added
  8. additionwas added
  9. extractionThe mixture was then extracted with Et2O (3×100 mL)
  10. dry with materialdried with Na2SO4
  11. concentrationconcentrated via rotovap to a solid crude
  12. customThe remaining crude was then immediately separated by silica gel (90% hexanes, 9% ethylacetate, 1% TEA, Rf=0.2)
  13. additionThe fractions containing the product
  14. concentrationconcentrated

Sources & evidence

ORD record
ord-5b7734cc1b90477a82e96ad051faa955
Source dataset
uspto-grants-2014_11
Patent number
US08895607B2

Reaction notes

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