Water → HCID 58788560, compound

HRID 1376288Notes

Reaction equation

HRID 1376288 reaction equation
[C:1]([O:4][C:5]1[C:6]([CH3:27])=[C:7]([CH:24]=[CH:25][CH:26]=1)[C:8]([NH:10][C@@H:11]([CH2:17][C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)[C@H:12]([OH:16])[C:13](O)=[O:14])=[O:9])(=[O:3])[CH3:2].[CH2:28]([NH:31][C:32]([C@@H:34]1[C:38]([CH3:40])([CH3:39])[S:37][CH2:36][NH:35]1)=[O:33])[CH:29]=[CH2:30].O.C(N=C=NC(C)C)(C)C>CC1CCCO1>[CH2:28]([NH:31][C:32]([C@@H:34]1[C:38]([CH3:40])([CH3:39])[S:37][CH2:36][N:35]1[C:13](=[O:14])[C@@H:12]([OH:16])[C@@H:11]([NH:10][C:8]([C:7]1[C:6]([CH3:27])=[C:5]([O:4][C:1](=[O:3])[CH3:2])[CH:26]=[CH:25][CH:24]=1)=[O:9])[CH2:17][C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)=[O:33])[CH:29]=[CH2:30]

Participants

6

Reactant 4

HCID 962WaterHCID 12734Diisopropylcarbodiimide2×HCID 15965808HCID 15965808, compoundHCID 59087778(2S,3S)-3-(3-acetoxy-2-methyl-benzoylamino)-2-hydroxy-4-phenyl-butyric acid

Product 1

HCID 58788560HCID 58788560, compound

Reagents, catalysts & solvents 1

HCID 73012-MethyltetrahydrofuranSolvent3×

Procedure

(2S,3S)-3-(3-Acetoxy-2-methyl-benzoylamino)-2-hydroxy-4-phenyl-butyric acid (271 g; 731 mmol) was added to a 5-L flask containing a solution of (4R)-5,5-Dimethyl-thiazolidine-4-carboxylic acid allylamide (161 g; 804 mmol) in 2-methyltetrahydrofuran (1.20 L total solution), while using 2-methyltetrahydrofuran (500 mL) for rinsing. HOBt.H2O (32.6 g; 241 mmol) was added, using 2-methyltetrahydrofuran (50 mL) for rinsing. The white suspension was allowed to stir at room temperature for 10 min. Diisopropylcarbodiimide (119 mL; 760 mmol) was added in three portions (40 mL+40 mL+39 mL) at 30 min intervals. One hour after the final DIC addition, Celite (100 g) was added and the suspension was allowed to stir at room temperature for 3 h. The mixture was vacuum-filtered, while 2-methyltetrahydrofuran (400 mL) was used to rinse over the solids and wash the resulting filter cake. The filtrate was transferred to 4-L separatory funnel, using 2-methyltetrahydrofuran (50 mL) for rinsing. The solution was washed with 1 N HCl (1.25 L), and then with an aqueous solution of NaHCO3 (27 g), NaCl (134 g) and H2O (1.25 L). The resulting organic phase was transferred to a 3-L distillation flask and the solution was then reduced to a volume of 1.12 L by distillation of 2-methyltetrahydrofuran at one atmosphere. The solution was then diluted with 2-methyltetrahydrofuran (230 mL) to bring the total volume to 1.35 L. After cooling the solution to 23° C., the solution of crude acetic acid 3-{(1 S,2S)-3-[(4R)-4-allylcarbamoyl-5,5-dimethyl-thiazolidin-3-yl]-1-benzyl-2-hydroxy-3-oxo-propylcarbamoyl}-2-methyl-phenyl ester on directly into the next step.

Workup

  1. washfor rinsing
  2. washfor rinsing
  3. additionwas added
  4. stirringto stir at room temperature for 3 h
  5. filtrationThe mixture was vacuum-filtered, while 2-methyltetrahydrofuran (400 mL)
  6. washto rinse over the solids
  7. washwash the resulting
  8. filtrationfilter cake
  9. washfor rinsing
  10. washThe solution was washed with 1 N HCl (1.25 L)
  11. distillationThe resulting organic phase was transferred to a 3-L distillation flask
  12. distillationthe solution was then reduced to a volume of 1.12 L by distillation of 2-methyltetrahydrofuran at one atmosphere
  13. additionThe solution was then diluted with 2-methyltetrahydrofuran (230 mL)
  14. temperatureAfter cooling the solution to 23° C.

Sources & evidence

ORD record
ord-a51facad61f14f4a82db959d560124ed
Source dataset
uspto-grants-2007_01
Patent number
US07169932B2

Reaction notes

Loading…