Water → {(1S,2S,4R)-4-(2,2-Dimethylpropylcarbamoyl)-1-[4-(2-chlorophenyl)-2,2-dimethyl-5-oxopiperazin-1-ylmethyl]-2-hydroxyheptyl}carbamic acid t-butyl ester

HRID 1695015Notes

Reaction equation

HRID 1695015 reaction equation
OC1C=CC=CN=1.[C:8]([O:12][C:13](=[O:42])[NH:14][C@H:15]([C@@H:33]1[CH2:37][C@@H:36]([CH2:38][CH2:39][CH3:40])[C:35](=[O:41])[O:34]1)[CH2:16][N:17]1[CH2:22][C:21](=[O:23])[N:20]([C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=2[Cl:30])[CH2:19][C:18]1([CH3:32])[CH3:31])([CH3:11])([CH3:10])[CH3:9].O.[CH3:44][C:45]([CH3:49])([CH3:48])[CH2:46][NH2:47]>>[C:8]([O:12][C:13](=[O:42])[NH:14][C@@H:15]([CH2:16][N:17]1[CH2:22][C:21](=[O:23])[N:20]([C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=2[Cl:30])[CH2:19][C:18]1([CH3:32])[CH3:31])[C@@H:33]([OH:34])[CH2:37][C@H:36]([C:35](=[O:41])[NH:47][CH2:46][C:45]([CH3:49])([CH3:48])[CH3:44])[CH2:38][CH2:39][CH3:40])([CH3:11])([CH3:9])[CH3:10]

Participants

5

Reactant 4

HCID 962WaterHCID 79882NeopentylamineHCID 66645802{(S)-2-[4-(2-Chlorophenyl)-2,2-dimethyl-5-oxopiperazin-1-yl]-1-[(2S,4R)-5-oxo-4-propyltetrahydrofuran-2-yl]ethyl}carbamic acid t-butyl esterHCID 178516071HCID 178516071, compound

Product 1

HCID 66645863{(1S,2S,4R)-4-(2,2-Dimethylpropylcarbamoyl)-1-[4-(2-chlorophenyl)-2,2-dimethyl-5-oxopiperazin-1-ylmethyl]-2-hydroxyheptyl}carbamic acid t-butyl esterYield 94%

Conditions

Temperature
80 °C

Procedure

3.8 mg of 2-hydroxypyridine (0.04 mmol) was added to a solution of 101 mg of {(S)-2-[4-(2-chlorophenyl)-2,2-dimethyl-5-oxopiperazin-1-yl]-1-[(2S,4R)-5-oxo-4-propyltetrahydrofuran-2-yl]ethyl}carbamic acid t-butyl ester obtained in Example (116i) (0.2 mmol) in (2,2-dimethylpropyl)amine (1 ml), and the mixture was stirred at 80° C. for five hours. The reaction mixture was cooled and then water was added, followed by extraction with ethyl acetate. Then, the organic layer was dried over anhydrous magnesium sulfate. After filtration, the solvent was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography (elution solvent:methylene chloride/methanol=30/1-20/1) to obtain 111 mg of the title compound (yield: 94%).

Workup

  1. temperatureThe reaction mixture was cooled
  2. extractionfollowed by extraction with ethyl acetate
  3. dry with materialThen, the organic layer was dried over anhydrous magnesium sulfate
  4. filtrationAfter filtration
  5. customthe solvent was evaporated under reduced pressure
  6. customthe residue was purified by silica gel column chromatography (elution solvent:methylene chloride/methanol=30/1-20/1)

Sources & evidence

ORD record
ord-72d5480e901345bc9b3a9dee4209fdc0
Source dataset
uspto-grants-2012_04
Patent number
US08158790B2

Reaction notes

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