tert-Butyldimethylsilane → HCID 58997402, compound

HRID 1592045Notes

Reaction equation

HRID 1592045 reaction equation
[CH2:1]([O:8][C:9](=[O:43])[C@@H:10]([NH:35]C(OC(C)(C)C)=O)[CH2:11][C:12]1[CH:17]=[CH:16][C:15]([N:18]2[CH2:22][C:21](=[O:23])[N:20](CC3C=CC(OC)=CC=3)[S:19]2(=[O:34])=[O:33])=[CH:14][CH:13]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C([SiH](C)C)(C)(C)C>C(O)(C(F)(F)F)=O>[CH2:1]([O:8][C:9](=[O:43])[C@@H:10]([NH2:35])[CH2:11][C:12]1[CH:17]=[CH:16][C:15]([N:18]2[CH2:22][C:21](=[O:23])[NH:20][S:19]2(=[O:34])=[O:33])=[CH:14][CH:13]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

4

Reactant 2

HCID 5072427tert-ButyldimethylsilaneHCID 67139408HCID 67139408, compound

Product 1

HCID 58997402HCID 58997402, compound

Reagents, catalysts & solvents 1

HCID 6422Trifluoroacetic acidSolvent

Conditions

Temperature
80 °C

Procedure

The title B compound, (S)-2-t-butoxycarbonylamino-3-{4-[5-(4-methoxy-benzyl)-1,1,4-trioxo-1,2,5-thiadiazolidin-2-yl]-phenyl}-propionic acid benzyl ester (40 mg, 0.066 mmol) is dissolved in TFA (1.32 mL) containing t-butyidimethylsilane (0.033 mL, 0.198 mmol) in a 1 dram vial. The reaction is monitored by reverse phase HPLC (YMC CombiScreen Pro C18, 50×4.6 mm I.D., particle size S-5 micron, 12 nM) eluting at 3 mL/min with a gradient of 90:10 (0.1% TFA in water:MeCN) to 10:90 at 7.0 min. Starting material has a retention time of 4.97 min and a new peak has a retention time of 3.09 min, the starting material without the t-butoxylcarbonyl group as an “intermediate”, [M+H]+=510. After 25 min at RT, the reaction is heated at 80° C. for an additional 25 min. A new peak by HPLC has a retention time of 2.02 min, corresponding to the desired product. The reaction is cooled, filtered through florisil to remove a black precipitate and concentrated on a Savant Speedvac. The resulting residue is triturated with Et2O to give a white solid. This material is purified on a preparative reverse phase HPLC column (YMC CombiPrep Pro C18, 50×20 mm I.D., particle size S-5 micron, 12 nM) in two equal aliquots and eluted at 30 mL/min with a gradient of 90:10 (0.1% TFA in water:MeCN) 10:90 over 5.0 min, then held at 10:90 until 7 min. Fractions containing product are combined and concentrated on a Savant Speedvac to yield (S)-2-amino-3-[4-(1,1,4-trioxo-1,2,5-thiadiazolidin-2-yl)-phenyl]-propionic acid benzyl ester as a white foam: [M−1]−=388.0.

Workup

  1. washeluting at 3 mL/min with a gradient of 90:10 (0.1% TFA in water:MeCN) to 10:90 at 7.0 min
  2. temperatureThe reaction is cooled
  3. filtrationfiltered through florisil
  4. customto remove a black precipitate
  5. concentrationconcentrated on a Savant Speedvac
  6. customThe resulting residue is triturated with Et2O
  7. customto give a white solid
  8. customThis material is purified on a preparative reverse phase HPLC column (YMC CombiPrep Pro C18, 50×20 mm I.D., particle size S-5 micron, 12 nM) in two equal aliquots
  9. washeluted at 30 mL/min with a gradient of 90:10 (0.1% TFA in water:MeCN) 10:90 over 5.0 min
  10. waitheld at 10:90 until 7 min
  11. additionFractions containing product
  12. concentrationconcentrated on a Savant Speedvac

Sources & evidence

ORD record
ord-60016993fbce496faf42fffa086c3162
Source dataset
uspto-grants-2007_11
Patent number
US07291635B2

Reaction notes

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