Acetic Acid → HCID 54577809, compound

HRID 1942752Notes

Reaction equation

HRID 1942752 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:12]2[S:16][C:15]([C:17]3[C:18]([CH3:26])=[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:27]1[CH2:32][CH2:31][CH:30]([C:33]([O:35]CC)=[O:34])[CH2:29][CH2:28]1.CC(O)=O.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[OH-].[Na+].Cl>ClCCl.CC(O)C>[Cl:1][C:2]1[CH:3]=[C:4]([C:12]2[S:16][C:15]([C:17]3[C:18]([CH3:26])=[C:19]([CH2:23][CH2:24][N:27]4[CH2:28][CH2:29][CH:30]([C:33]([OH:35])=[O:34])[CH2:31][CH2:32]4)[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

9

Reactant 6

HCID 176Acetic AcidHCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 70770Ethyl 4-piperidinecarboxylateHCID 5049666Sodium triacetoxyborohydrideHCID 58494069HCID 58494069, compound

Product 1

HCID 54577809HCID 54577809, compoundYield 52.5%

Reagents, catalysts & solvents 2

HCID 3776IsopropanolSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of [3-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,3,4-thiadiazol-2-yl)-2-methylphenyl]acetaldehyde (118 mg, 0.305 mmol) (D97) in Dichloromethane (DCM) (20 mL) stirred at room temperature was added ethyl 4-piperidinecarboxylate (192 mg, 1.220 mmol) and AcOH (0.15 mL, 2.62 mmol). The reaction mixture was stirred at room temperature for 10 min, and sodium triacetoxyborohydride (129 mg, 0.610 mmol) was added. The reaction mixture was continuously stirred for 1 day. The reaction was quenched with water, and DCM was evaporated in vacuo. Sodium hydroxide (12.20 mg, 0.305 mmol) and i-PrOH was added. The reaction mixture was continuously stirred for 2 hours. 1M HCl solution was added until PH=6-7. i-PrOH was evaporated in vacuo. The aqueous layers were extracted by EA/THF for 3 times. The combined 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-methylphenyl]ethyl}-4-piperidinecarboxylic acid (E58) (80 mg) as a off-white solid. δH (DMSO-d6, 400 MHz): 1.35 (6H, d), 1.55 (2H, m), 1.81 (2H, m), 2.05 (2H, t), 2.18 (1H, tt), 2.41 (3H, s), 2.45 (2H, m), 2.87 (4H, m), 4.83 (1H, dt), 7.30 (1H, m), 7.41 (3H, m), 7.94 (1H, dd), 8.08 (1H, d). MS (ES): C26H30ClN3O3S requires 499.2. found 500.2 (M+H+).

Workup

  1. stirringThe reaction mixture was continuously stirred for 1 day
  2. customThe reaction was quenched with water, and DCM
  3. customwas evaporated in vacuo
  4. stirringThe reaction mixture was continuously stirred for 2 hours
  5. customi-PrOH was evaporated in vacuo
  6. extractionThe aqueous layers were extracted by EA/THF for 3 times
  7. concentrationThe combined organic layers were concentrated
  8. custompurified by Mass Directed AutoPrep

Sources & evidence

ORD record
ord-2e397933afde4d229f99ad105740a927
Source dataset
uspto-grants-2013_03
Patent number
US08389508B2

Reaction notes

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