Neopentylamine → {(1S,2S,4R)-4-(2,2-Dimethylpropylcarbamoyl)-1-[4-(2-chloro-5-fluorophenyl)-2,2-dimethyl-5-oxopiperazin-1-ylmethyl]-2-hydroxypentyl}carbamic acid t-butyl ester

HRID 1694977Notes

Reaction equation

HRID 1694977 reaction equation
OC1C=CC=CN=1.[C:8]([O:12][C:13](=[O:41])[NH:14][C@H:15]([C@@H:34]1[CH2:38][C@@H:37]([CH3:39])[C:36](=[O:40])[O:35]1)[CH2:16][N:17]1[CH2:22][C:21](=[O:23])[N:20]([C:24]2[CH:29]=[C:28]([F:30])[CH:27]=[CH:26][C:25]=2[Cl:31])[CH2:19][C:18]1([CH3:33])[CH3:32])([CH3:11])([CH3:10])[CH3:9].[CH3:42][C:43]([CH3:47])([CH3:46])[CH2:44][NH2:45]>O>[C:8]([O:12][C:13](=[O:41])[NH:14][C@@H:15]([CH2:16][N:17]1[CH2:22][C:21](=[O:23])[N:20]([C:24]2[CH:29]=[C:28]([F:30])[CH:27]=[CH:26][C:25]=2[Cl:31])[CH2:19][C:18]1([CH3:32])[CH3:33])[C@@H:34]([OH:35])[CH2:38][C@H:37]([C:36](=[O:40])[NH:45][CH2:44][C:43]([CH3:47])([CH3:46])[CH3:42])[CH3:39])([CH3:9])([CH3:11])[CH3:10]

Participants

5

Reactant 3

HCID 79882NeopentylamineHCID 66645673{(S)-2-[4-(2-Chloro-5-fluorophenyl)-2,2-dimethyl-5-oxopiperazin-1-yl]-1-[(2S,4R)-4-methyl-5-oxotetrahydrofuran-2-yl]ethyl}carbamic acid t-butyl esterHCID 178516071HCID 178516071, compound

Product 1

HCID 66645689{(1S,2S,4R)-4-(2,2-Dimethylpropylcarbamoyl)-1-[4-(2-chloro-5-fluorophenyl)-2,2-dimethyl-5-oxopiperazin-1-ylmethyl]-2-hydroxypentyl}carbamic acid t-butyl esterYield 93%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
80 °C

Procedure

20 mg of 2-hydroxypyridine (0.21 mmol) was added to a solution of 210 mg of {(S)-2-[4-(2-chloro-5-fluorophenyl)-2,2-dimethyl-5-oxopiperazin-1-yl]-1-[(2S,4R)-4-methyl-5-oxotetrahydrofuran-2-yl]ethyl}carbamic acid t-butyl ester obtained in Example (97b) (0.42 mmol) in (2,2-dimethylpropyl)amine (0.74 ml) (6.30 mmol), and the mixture was stirred at 80° C. for two hours. The reaction mixture was cooled and then water was added, followed by extraction with methylene chloride. 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/acetone=5/2-2/1) to obtain 228 mg of the title compound (yield: 93%).

Workup

  1. temperatureThe reaction mixture was cooled
  2. extractionfollowed by extraction with methylene chloride
  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/acetone=5/2-2/1)

Sources & evidence

ORD record
ord-6b88d4792dbd479896fdd0f76ed28a3c
Source dataset
uspto-grants-2012_04
Patent number
US08158790B2

Reaction notes

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