Acetyl chloride → HCID 21101989, compound

HRID 1353174Notes

Reaction equation

HRID 1353174 reaction equation
[C:1](Cl)(=O)[CH3:2].[CH2:5]([N:12]1[CH2:17][CH:16]([N:18]([S:25]([C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)(=[O:27])=[O:26])[C:19](C(C)(C)C)=[O:20])[CH2:15][CH:14]([NH:34][C:35](=[O:41])OC(C)(C)C)[C:13]1=[O:42])[C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1.C(=O)([O-])[O-:44].[Na+].[Na+].[C:49](Cl)(=O)[C:50]1[CH:55]=CC=C[CH:51]=1.[CH2:58]1[CH2:62]O[CH2:60][CH2:59]1>O.CO>[C:35]([NH:34][CH:14]1[C:13](=[O:42])[N:12]([CH2:5][C:6]2[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=2)[CH2:17][CH:16]([N:18]([S:25]([C:28]2[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=2)(=[O:26])=[O:27])[C:19](=[O:20])[O:44][C:50]([CH3:49])([CH3:51])[CH3:55])[CH2:15]1)(=[O:41])[C:58]1[CH:59]=[CH:60][CH:2]=[CH:1][CH:62]=1

Participants

8

Reactant 5

HCID 6367Acetyl chlorideHCID 7412Benzoyl chlorideHCID 8028TetrahydrofuranHCID 10340Sodium CarbonateHCID 69426142HCID 69426142, compound

Product 1

HCID 21101989HCID 21101989, compound

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent

Procedure

Acetyl chloride (1.0 mL) is added dropwise to methanol at 0° C. over 2 min. The solution was stirred, warmed to room temperature for 30 min and then transferred by pipette to a solution of compound 1G (34 mg, 0.061 mmol) and stirred for 1 h. The reaction mixture was evaporated and stirred with a mixture of 2 M sodium carbonate solution (1 mL, 2 mmol) and a 1:1 solution of benzoyl chloride and THF (21 μL, 0.094 mmol). After 14 h, the reaction mixture was diluted with water (3 mL) and extracted three times with EtOAc. The organic extracts were dried (MgSO4), filtered and evaporated to give tert-butyl 5-benzamido-1-benzyl-6-oxopiperidin-3-yl(phenylsulfonyl)carbamate as a colorless oil. The product described above was dissolved in CH2Cl2 (1 mL) at room temperature and trifluoroacetic acid (0.5 mL) was added. After evaporation the residue was purified by preparative reverse-phase chromatography (YMC S5 ODS 30×100 mm column, H2O/acetonitrile, 0.1% TFA gradient) to give N-(1-benzyl-2-oxo-5-(phenylsulfonamido)piperidin-3-yl)benzamide as a colorless gum (14.5 mg, 51%). The product described above (14.5 mg, 0.031 mmol) was stirred in pyridine (2.0 mL) at room temperature under argon and treated with Lawesson's reagent (25.3 mg, 0.063 mmol). The mixture was heated to reflux for 4 h, cooled to room temperature and an additional portion of Lawesson's reagent (15 mg) was added. After 15 h, additional Lawesson's reagent (20 mg) was added. After an additional 24 h, the reaction mixture was cooled, evaporated and partitioned between water and EtOAc. The organic phase was evaporated and the foul-smelling residue was purified by gravity chromatography on silica gel (1:5 EtOAc/CH2Cl2) to give the title compound as an odorless yellow oil (9.7 mg, 68% yield). MS [M+H]+: found 462. HPLC (Method A): retention time, 6.45 min; 95.4% purity. 1H NMR (CDCl3, 400 MHz) δ 7.81 (m, 2H), 7.70 (m, 2H), 7.53 (m, 1H), 7.46 (m, 2H), 7.39–7.30 (m, 8H), 5.01 (d, 1H, J=8.8 Hz), 4.27 (s, 2H), 3.94 (m, 1H), 3.11–2.95 (m, 3H), 2.71 (dd, 1H, J=3.1, 16.2 Hz); 13C NMR (CDCl3, 101 MHz) δ152.6, 144.8, 140.8, 135.9, 134.0, 132.7, 129.2, 128.9, 128.8, 128.7, 128.6, 126.8, 125.2, 60.6, 53.1, 46.7, 32.0.

Workup

  1. stirringstirred for 1 h
  2. customThe reaction mixture was evaporated
  3. extractionextracted three times with EtOAc
  4. dry with materialThe organic extracts were dried (MgSO4)
  5. filtrationfiltered
  6. customevaporated

Sources & evidence

ORD record
ord-5a90eda8d34f415dbd5f933ded77442d
Source dataset
uspto-grants-2007_05
Patent number
US07220859B2

Reaction notes

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