Formaldehyde → ethyl 5-({[(2R)-2-(hydroxymethyl)-5-oxopyrrolidine-1-yl]methyl}thio)pentanoate

HRID 853838Notes

Reaction equation

HRID 853838 reaction equation
[Si]([O:8][CH2:9][C@@H:10]1[NH:14][C:13](=[O:15])[CH2:12][CH2:11]1)(C(C)(C)C)(C)C.O.[C:17]1(C)C=CC(S(O)(=O)=O)=CC=1.C=O.[SH:30][CH2:31][CH2:32][CH2:33][CH2:34][C:35]([O:37][CH2:38][CH3:39])=[O:36]>C1C=CC=CC=1.C(OC)(C)(C)C>[OH:8][CH2:9][C@H:10]1[CH2:11][CH2:12][C:13](=[O:15])[N:14]1[CH2:17][S:30][CH2:31][CH2:32][CH2:33][CH2:34][C:35]([O:37][CH2:38][CH3:39])=[O:36]

Participants

7

Reactant 4

HCID 712FormaldehydeHCID 521998p-Toluenesulfonic acid monohydrateHCID 13771167(R)-5-(((tert-Butyldimethylsilyl)oxy)methyl)pyrrolidin-2-oneHCID 15210849Ethyl 5-mercaptopentanoate

Product 1

HCID 69237585ethyl 5-({[(2R)-2-(hydroxymethyl)-5-oxopyrrolidine-1-yl]methyl}thio)pentanoateYield 0.4%

Reagents, catalysts & solvents 2

HCID 241BenzeneSolventHCID 15413tert-Butyl methyl etherSolvent

Procedure

Under atmosphere of argon, a solution of (5R)-5-({[tert-butyl(dimethyl)silyl]oxy}methyl)pyrrolidine-2-one (2 g) in benzene (20 mL) was added by p-toluene sulfonic acid monohydrate (166 mg) and paraformic aldehyde (290 mg) and stirred for an hour at the room temperature. The mixture was added by ethyl 5-mercaptopentanoate (1.41 g) and stirred heating using Dean-Stark apparatus for three hours at the temperature of 125° C. The mixture was diluted with tert-butylmethylether solution, washed with water and saturated brine, dried over an sodium sulfate, concentrated and purified by column chromatography on silica gel (ethyl acetate:hexane=1:6). Under atmosphere of argon, the purified compound (1.9 g) in tetrahyrdorfuran solution (1.5 mL) was added by 1M tetrabutylammonium fluoride in tetrahydrofuran (4.7 mL) and stirred for an hour at room temperature. The mixture was diluted with ethyl acetate and washed with water and saturated brine. The organic layer was dried over sodium sulfate, concentrated and purified by column chromatography on silica gel (ethyl acetate:hexane=1:2) to give the title compound (1.05 mg) having the following physical data.

Workup

  1. stirringstirred
  2. temperatureheating
  3. customfor three hours
  4. customat the temperature of 125° C
  5. washwashed with water and saturated brine
  6. dry with materialdried over an sodium sulfate
  7. concentrationconcentrated
  8. custompurified by column chromatography on silica gel (ethyl acetate:hexane=1:6)
  9. additionUnder atmosphere of argon, the purified compound (1.9 g) in tetrahyrdorfuran solution (1.5 mL) was added by 1M tetrabutylammonium fluoride in tetrahydrofuran (4.7 mL)
  10. stirringstirred for an hour at room temperature
  11. additionThe mixture was diluted with ethyl acetate
  12. washwashed with water and saturated brine
  13. dry with materialThe organic layer was dried over sodium sulfate
  14. concentrationconcentrated
  15. custompurified by column chromatography on silica gel (ethyl acetate:hexane=1:2)

Sources & evidence

ORD record
ord-d4aaa04cab45424e9fc464e7c53013c2
Source dataset
uspto-grants-2007_08
Patent number
US07256211B1

Reaction notes

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