Sodium cyanoborohydride → 5-(4-{2(R)-[2(R)-(3-chlorophenyl)-2-t-butyldimethylsilyloxyethylamino]propoxy}benzyl)thiazolidine-2,4-dione

HRID 1648446Notes

Reaction equation

HRID 1648446 reaction equation
FC(F)(F)C(O)=O.[NH2:8][C@H:9]([CH3:26])[CH2:10][O:11][C:12]1[CH:25]=[CH:24][C:15]([CH2:16][CH:17]2[S:21][C:20](=[O:22])[NH:19][C:18]2=[O:23])=[CH:14][CH:13]=1.[Si:27]([O:34][C@H:35]([C:38]1[CH:43]=[CH:42][CH:41]=[C:40]([Cl:44])[CH:39]=1)[CH:36]=O)([C:30]([CH3:33])([CH3:32])[CH3:31])([CH3:29])[CH3:28].C([BH3-])#N.[Na+]>CO>[Cl:44][C:40]1[CH:39]=[C:38]([C@@H:35]([O:34][Si:27]([C:30]([CH3:31])([CH3:33])[CH3:32])([CH3:29])[CH3:28])[CH2:36][NH:8][C@H:9]([CH3:26])[CH2:10][O:11][C:12]2[CH:25]=[CH:24][C:15]([CH2:16][CH:17]3[S:21][C:20](=[O:22])[NH:19][C:18]3=[O:23])=[CH:14][CH:13]=2)[CH:43]=[CH:42][CH:41]=1

Participants

5

Reactant 3

HCID 5003444Sodium cyanoborohydrideHCID 11129841(R)-2-[(tert-Butyldimethylsilyl)oxy]-2-(3-chlorophenyl)acetaldehydeHCID 228549835-{4-[2(R)-Aminopropoxy]benzyl}thiazolidine-2,4-dione trifluoroacetate

Product 1

HCID 882931375-(4-{2(R)-[2(R)-(3-chlorophenyl)-2-t-butyldimethylsilyloxyethylamino]propoxy}benzyl)thiazolidine-2,4-dioneYield 91.5%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A mixture of 36.5 g of 5-{4-[2(R)-aminopropoxy]benzyl}thiazolidine-2,4-dione trifluoroacetate [prepared as described in Preparation 2], 98.4 g of (R)-α-(t-butyldimethylsilyloxy)-α-(3-chlorophenyl)acetaldehyde [prepared as described in Preparation 12] and 400 ml of absolute methanol was stirred at room temperature for 2.5 hours, after which the mixture was cooled using a salted ice-bath. 29.0 g of sodium cyanoborohydride were then added to the mixture in small portions, and the mixture was allowed to stand overnight at room temperature. At the end of this time, the methanol was distilled off under reduced pressure, the residue was mixed with water and ethyl acetate, and the ethyl acetate layer was separated from the mixture. The ethyl acetate layer was then washed with a saturated aqueous solution of sodium chloride, after which it was dried over anhydrous sodium sulfate. The solvent was then distilled off under reduced pressure. The residue was purified by column chromatography through silica gel, using a 2:1 by volume mixture of ethyl acetate and hexane as the eluent, to give 46.5 g of the title compound.

Workup

  1. temperatureafter which the mixture was cooled
  2. waitto stand overnight at room temperature
  3. distillationAt the end of this time, the methanol was distilled off under reduced pressure
  4. additionthe residue was mixed with water and ethyl acetate
  5. customthe ethyl acetate layer was separated from the mixture
  6. washThe ethyl acetate layer was then washed with a saturated aqueous solution of sodium chloride
  7. dry with materialafter which it was dried over anhydrous sodium sulfate
  8. distillationThe solvent was then distilled off under reduced pressure
  9. customThe residue was purified by column chromatography through silica gel
  10. additionby volume mixture of ethyl acetate and hexane as the eluent

Sources & evidence

ORD record
ord-c8f957282934466c91fb239ce987a7d3
Source dataset
uspto-grants-1995_07
Patent number
US05436257

Reaction notes

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