tert-Butyldimethylsilane → HCID 58997415, compound

HRID 1592046Notes

Reaction equation

HRID 1592046 reaction equation
C(OC([NH:8][C@@H:9]([CH2:13][C:14]1[CH:19]=[CH:18][C:17]([N:20]2[CH2:24][C:23](=[O:25])[N:22](CC3C=CC(OC)=CC=3)[S:21]2(=[O:36])=[O:35])=[CH:16][CH:15]=1)[C:10]([OH:12])=[O:11])=O)(C)(C)C.C([SiH](C)C)(C)(C)C>C(O)(C(F)(F)F)=O>[NH2:8][C@@H:9]([CH2:13][C:14]1[CH:19]=[CH:18][C:17]([N:20]2[CH2:24][C:23](=[O:25])[NH:22][S:21]2(=[O:35])=[O:36])=[CH:16][CH:15]=1)[C:10]([OH:12])=[O:11]

Participants

4

Reactant 2

HCID 5072427tert-ButyldimethylsilaneHCID 67138881HCID 67138881, compound

Product 1

HCID 58997415HCID 58997415, compound

Reagents, catalysts & solvents 1

HCID 6422Trifluoroacetic acidSolvent

Conditions

Temperature
80 °C

Procedure

The title A compound, (S)-2-t-butoxycarbonylamino-3-(4-[5-(4-methoxy-benzyl)-1,1,4-trioxo-1,2,5-thiadiazolidin-2-yl]-phenyl)-propionic acid (84.5 mg, 0.163 mmol) is dissolved in TFA (3.26 mL) containing t-butyidimethylsilane (0.081 mL, 0.498 mmol) at RT. 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 over 7.0 min. The starting material has a retention time of 3.85 min. After 20 min at RT, the reaction is heated at 80° C. for an additional 45 min. A new peak by HPLC has a retention time of 0.52 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 100:0 (0.1% TFA in water:MeCN) to 70:30 over 5.0 min, then to 10:90 by 7 min. Fractions containing product are combined and concentrated on a Savant Speedvac, then triturated with 10% dimethylsulfoxide (DMSO) in MeCN to yield (S)-2-amino-3-[4-(1,1,4-trioxo-1,2,5-thiadiazolidin-2-yl)-phenyl]-propionic acid as a white solid: [M−1]−=298.0.

Workup

  1. washeluting at 3 mL/min with a gradient of 90:10 (0.1% TFA in water:MeCN) to 10:90 over 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 100:0 (0.1% TFA in water:MeCN) to 70:30 over 5.0 min
  10. waitto 10:90 by 7 min
  11. additionFractions containing product
  12. concentrationconcentrated on a Savant Speedvac
  13. customtriturated with 10% dimethylsulfoxide (DMSO) in MeCN

Sources & evidence

ORD record
ord-a2f110d525114b9bb2cbcf0eb5a9320e
Source dataset
uspto-grants-2007_11
Patent number
US07291635B2

Reaction notes

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