Acetic Acid → HCID 54577585, compound

HRID 1942751Notes

Reaction equation

HRID 1942751 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:12]2[S:16][C:15]([C:17]3[C:18]([CH2:26][CH3:27])=[C:19]([CH2:23][CH:24]=O)[CH:20]=[CH:21][CH:22]=3)=[N:14][N:13]=2)[CH:5]=[CH:6][C:7]=1[O:8][CH:9]([CH3:11])[CH3:10].[NH:28]1[CH2:36][CH2:35][CH2:34][C@H:29]1[C:30]([O:32]C)=[O:31].CC(O)=O.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[OH-].[Na+]>ClCCl>[Cl:1][C:2]1[CH:3]=[C:4]([C:12]2[S:16][C:15]([C:17]3[C:18]([CH2:26][CH3:27])=[C:19]([CH2:23][CH2:24][N:28]4[CH2:36][CH2:35][CH2:34][C@H:29]4[C:30]([OH:32])=[O:31])[CH:20]=[CH:21][CH:22]=3)=[N:14][N:13]=2)[CH:5]=[CH:6][C:7]=1[O:8][CH:9]([CH3:11])[CH3:10]

Participants

7

Reactant 5

HCID 176Acetic AcidHCID 14798Sodium HydroxideHCID 853477Methyl L-prolinateHCID 5049666Sodium triacetoxyborohydrideHCID 58494137HCID 58494137, compound

Product 1

HCID 54577585HCID 54577585, compoundYield 21.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of [3-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,3,4-thiadiazol-2-yl)-2-ethylphenyl]acetaldehyde (90 mg, 0.224 mmol) (D15) in Dichloromethane (DCM) (20 mL) stirred at room temperature was added methyl L-prolinate (149 mg, 0.898 mmol) and AcOH (0.15 mL, 2.62 mmol). The reaction mixture was stirred at room temperature for 10 min, and sodium triacetoxyborohydride (110 mg, 0.522 mmol) was added. The reaction mixture was continuously stirred overnight. The reaction was quenched with water, and EtOH was evaporated in vacuo. i-PrOH was added, followed by sodium hydroxide (8.98 mg, 0.224 mmol). The reaction mixture was stirred for another 2 hours. i-PrOH was evaporated in vacuo. The aqeuous layer was extracted by EA/THF for 3 times. The combined organic solution was washed by brine. The organic layers were concentrated, and purified by Mass Directed AutoPrep to afford 1-{2-[3-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,3,4-thiadiazol-2-yl)-2-ethylphenyl]ethyl}-L-proline (E52) (24 mg) as a off-white solid.

Workup

  1. waitThe reaction mixture was continuously stirred overnight
  2. customThe reaction was quenched with water, and EtOH
  3. customwas evaporated in vacuo
  4. additioni-PrOH was added
  5. stirringThe reaction mixture was stirred for another 2 hours
  6. customi-PrOH was evaporated in vacuo
  7. extractionThe aqeuous layer was extracted by EA/THF for 3 times
  8. washThe combined organic solution was washed by brine
  9. concentrationThe organic layers were concentrated
  10. custompurified by Mass Directed AutoPrep

Sources & evidence

ORD record
ord-f368298e60b8445b9c83d65d3d7a3564
Source dataset
uspto-grants-2013_03
Patent number
US08389508B2

Reaction notes

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