Hydrochloric Acid → (3aS,6aR)-hexahydro-1-[(R)-(1-phenylethyl)]-2-oxo-3-benzylthieno[3,4-d]imidazol-4-ylidene pentanoic acid

HRID 232444

Reaction equation

HRID 232444 reaction equation
[H-].[Na+].[H][H].[Br-].[C:6]([CH2:9][CH2:10][CH2:11][CH2:12][P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)([OH:8])=[O:7].[C:32]1([C@H:38]([N:40]2[C@H:44]3[CH2:45][S:46][C:47](=O)[C@H:43]3[N:42]([CH2:49][C:50]3[CH:55]=[CH:54][CH:53]=[CH:52][CH:51]=3)[C:41]2=[O:56])[CH3:39])[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1.Cl>CS(C)=O.C1(C)C=CC=CC=1.C(OCC)(=O)C.C1C=CC=CC=1.O>[C:32]1([C@H:38]([N:40]2[C@H:44]3[CH2:45][S:46][C:47](=[C:9]([CH2:10][CH2:11][CH3:12])[C:6]([OH:8])=[O:7])[C@H:43]3[N:42]([CH2:49][C:50]3[CH:51]=[CH:52][CH:53]=[CH:54][CH:55]=3)[C:41]2=[O:56])[CH3:39])[CH:33]=[CH:34][CH:35]=[CH:36][CH:37]=1

Participants

11

Reactant 5

HCID 313Hydrochloric AcidHCID 24758Sodium hydrideHCID 161236(4-Carboxybutyl)triphenylphosphonium bromideHCID 11013605(3aS,6aR)-1-[(R)-(1-phenylethyl)]-3-benzyl-dihydro-1H-thieno[3,4-d]-imidazol-2,4(3H,3aH)-dioneHCID 178418361HCID 178418361, compound

Product 1

HCID 86743268(3aS,6aR)-hexahydro-1-[(R)-(1-phenylethyl)]-2-oxo-3-benzylthieno[3,4-d]imidazol-4-ylidene pentanoic acid

Reagents, catalysts & solvents 5

HCID 241BenzeneSolventHCID 679Dimethyl SulfoxideSolvent3×HCID 962WaterSolventHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
70 °C

Procedure

159.8 mg (3.66 mmol) of sodium hydride and 1.7 ml of dimethyl sulfoxide were placed in a 25-ml round-bottom flask. The suspension was heated with stirring and under argon to 70° C. It was stirred for 40 minutes more until evolution of hydrogen was complete. The solution was cooled to room temperature and a solution of 801.5 mg (1.8 mmol) of (4-carboxybutyl)-triphenylphosphonium bromide in 1 ml of dimethyl sulfoxide was added. The dark red reaction mixture was stirred for 15 minutes and then added dropwise to a solution of 271 mg (0.77 mmol) of (3as,6aR)-1-[(R)-(1-phenylethyl)]-3-benzyl-dihydro-1H-thieno[3,4-d]-imidazol-2,4(3H,3aH)-dione in 2 ml of dimethyl sulfoxide and 0.2 ml of toluene. The reaction mixture was stirred for 2 hours at room temperature. Then 1 g of ice, 1 ml of conc, HCl and again 9 g of ice were added. After 5 minutes, 5 ml of water, 10 ml of benzene and 5 ml of ethyl acetate were added. Then the mixture was stirred for 1 hour at 60° C. The phases were separated. The brown organic phase was dried with 5 g of magnesium sulfate and separated with 4 preparative silica gel thin-layer plates (1 mm) by means of ethyl acetate. The product, (3aS, 6aR)-hexahydro-1-[(R)-(1-phenylethyl)]-2-oxo-3-benzylthieno[3,4-d]-imidazol-4-ylidene pentanoic acid, a colorless oil, was obtained in a yield of 38.2 mg (12 percent). Concerning the product:

Workup

  1. temperatureThe suspension was heated
  2. temperatureThe solution was cooled to room temperature
  3. customThe dark red reaction mixture
  4. stirringwas stirred for 15 minutes
  5. stirringThe reaction mixture was stirred for 2 hours at room temperature
  6. stirringThen the mixture was stirred for 1 hour at 60° C
  7. customThe phases were separated
  8. dry with materialThe brown organic phase was dried with 5 g of magnesium sulfate
  9. customseparated with 4 preparative silica gel thin-layer plates (1 mm) by means of ethyl acetate

Sources & evidence

ORD record
ord-a739537c732e46d2b401686ea9f762a8
Source dataset
uspto-grants-1989_07
Patent number
US04851540

Linked notes

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