Ethyl formate → HCID 59468952, compound

HRID 1690113Notes

Reaction equation

HRID 1690113 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[CH2:8][O:9][C:10]1[CH:15]=[CH:14][C:13]([C@@H:16]2[N:20]([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[C@H:19]([C:28]([O:30][CH3:31])=[O:29])[CH2:18][CH2:17]2)=[CH:12][C:11]=1[O:32][CH3:33].[Li+].C[Si]([N-][Si](C)(C)C)(C)C.[CH:44](OCC)=[O:45].[BH4-].[Na+]>C1COCC1>[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[CH2:8][O:9][C:10]1[CH:15]=[CH:14][C:13]([C@@H:16]2[N:20]([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[C@:19]([CH2:44][OH:45])([C:28]([O:30][CH3:31])=[O:29])[CH2:18][CH2:17]2)=[CH:12][C:11]=1[O:32][CH3:33]

Participants

6

Reactant 4

HCID 8025Ethyl formateHCID 2733832Lithium HexamethyldisilazideHCID 4311764Sodium borohydrideHCID 59468928HCID 59468928, compound

Product 1

HCID 59468952HCID 59468952, compoundYield 46%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-40 °C

Procedure

To a solution of 1-(1,1-dimethylethyl) 2-methyl (2S,5R)-5-[4-{[(2-fluorophenyl)methyl]oxy}-3-(methyloxy)phenyl]-1,2-pyrrolidinedicarboxylate (D58, 0.35 g, 0.76 mmol) in dry THF (6 ml) at −78° C. was added dropwise LiHMDS (0.80 ml, 0.80 mmol, 1M solution in THF). The mixture was allowed to warm to −40° C. and was stirred for 40 min at that temperature. Then the mixture was again cooled to −78° C. and ethyl formate (1.23 ml, 15.2 mmol) was added. The mixture was left stirring for another 8 h at the same temperature. The reaction was quenched with brine, diluted with water and extracted with ethyl acetate. The organic layer was dried (Na2SO4), filtered and evaporated. The crude material was dissolved in MeOH (5 ml) at 0° C. and NaBH4 (30 mg, 0.79 mmol) was added. The mixture was stirred for 1 h at the same temperature. The reaction was quenched with a 5% solution of aqueous NaHCO3, diluted with water and extracted with ethyl acetate. The organic layer was dried (Na2SO4), filtered and evaporated and the residue was purified by chromatography on silica gel using cyclohexane and ethyl acetate (9:1 to 75:25) to afford the title compound as a colourless oil (170 mg, 46%); Rt (HPLC): 5.78 min; MS: (ES/+) m/z: 512 [M+Na] C26H32FNO7 requires 489.

Workup

  1. temperatureThen the mixture was again cooled to −78° C.
  2. waitThe mixture was left
  3. stirringstirring for another 8 h at the same temperature
  4. customThe reaction was quenched with brine
  5. additiondiluted with water
  6. extractionextracted with ethyl acetate
  7. dry with materialThe organic layer was dried (Na2SO4)
  8. filtrationfiltered
  9. customevaporated
  10. dissolutionThe crude material was dissolved in MeOH (5 ml) at 0° C.
  11. stirringThe mixture was stirred for 1 h at the same temperature
  12. customThe reaction was quenched with a 5% solution of aqueous NaHCO3
  13. additiondiluted with water
  14. extractionextracted with ethyl acetate
  15. dry with materialThe organic layer was dried (Na2SO4)
  16. filtrationfiltered
  17. customevaporated
  18. customthe residue was purified by chromatography on silica gel

Sources & evidence

ORD record
ord-29f495264a0d404787892622e67afe46
Source dataset
uspto-grants-2012_04
Patent number
US08153623B2

Reaction notes

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