4-Nitrophenyl chloroformate → (R)-2-(4-amino-3-chloro-5-trifluoromethyl-phenyl)-1-ethoxycarbonyl-ethyl 4-(2-oxo-1,2,4,5-tetrahydro-benzo[d][1,3]diazepin-3-yl)-piperidine-1-carboxylate

HRID 2116682Notes

Reaction equation

HRID 2116682 reaction equation
Cl[C:2](OC1C=CC([N+]([O-])=O)=CC=1)=[O:3].[NH2:14][C:15]1[C:20]([C:21]([F:24])([F:23])[F:22])=[CH:19][C:18]([CH2:25][C@@H:26]([OH:32])[C:27]([O:29][CH2:30][CH3:31])=[O:28])=[CH:17][C:16]=1[Cl:33].[NH:34]1[CH2:39][CH2:38][CH:37]([N:40]2[CH2:46][CH2:45][C:44]3[CH:47]=[CH:48][CH:49]=[CH:50][C:43]=3[NH:42][C:41]2=[O:51])[CH2:36][CH2:35]1>CN(C1C=CN=CC=1)C.N1C=CC=CC=1>[O:51]=[C:41]1[NH:42][C:43]2[CH:50]=[CH:49][CH:48]=[CH:47][C:44]=2[CH2:45][CH2:46][N:40]1[CH:37]1[CH2:36][CH2:35][N:34]([C:2]([O:32][C@@H:26]([C:27]([O:29][CH2:30][CH3:31])=[O:28])[CH2:25][C:18]2[CH:19]=[C:20]([C:21]([F:22])([F:23])[F:24])[C:15]([NH2:14])=[C:16]([Cl:33])[CH:17]=2)=[O:3])[CH2:39][CH2:38]1

Participants

6

Reactant 3

HCID 821294-Nitrophenyl chloroformateHCID 113795873-(Piperidin-4-yl)-4,5-dihydro-1H-benzo[d][1,3]diazepin-2(3H)-oneHCID 66941933ethyl (R)-3-(4-amino-3-chloro-5-trifluoromethyl-phenyl)-2-hydroxy-propionate

Product 1

HCID 69195689(R)-2-(4-amino-3-chloro-5-trifluoromethyl-phenyl)-1-ethoxycarbonyl-ethyl 4-(2-oxo-1,2,4,5-tetrahydro-benzo[d][1,3]diazepin-3-yl)-piperidine-1-carboxylate

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 1049PyridineSolvent2×

Procedure

5.2 g (25.6 mmol) 4-nitrophenyl chloroformate were added under protective nitrogen gas to a mixture of 3.1 g (25.6 mmol) DMAP and 70 ml of pyridine and stirred for 1.5 hours at ambient temperature. Then 8.0 g (25.7 mmol) ethyl (R)-3-(4-amino-3-chloro-5-trifluoromethyl-phenyl)-2-hydroxy-propionate, dissolved in 30 ml of pyridine, were slowly added dropwise at ambient temperature, the reaction mixture was stirred for 2 hours at ambient temperature, 6.3 g (25.6 mmol) 3-piperidin-4-yl-1,3,4,5-tetrahydro-1,3-benzdiazepin-2-one were added as a solid substance and the mixture was stirred overnight at ambient temperature. The reaction mixture was evaporated down under reduced pressure and distributed between 200 ml of ethyl acetate and 200 ml aqueous 10% citric acid solution. The organic phase washed twice with 200 ml 10% citric acid solution and five times with 150 ml 15% aqueous potassium carbonate solution, dried over sodium sulphate and evaporated down under reduced pressure. The residue was purified by column chromatography.

Workup

  1. additionwere slowly added dropwise at ambient temperature
  2. stirringthe reaction mixture was stirred for 2 hours at ambient temperature
  3. stirringthe mixture was stirred overnight at ambient temperature
  4. customThe reaction mixture was evaporated down under reduced pressure
  5. washThe organic phase washed twice with 200 ml 10% citric acid solution and five times with 150 ml 15% aqueous potassium carbonate solution
  6. dry with materialdried over sodium sulphate
  7. customevaporated down under reduced pressure
  8. customThe residue was purified by column chromatography

Sources & evidence

ORD record
ord-6f4cd9fd612d4f4c8338a9be174f27ee
Source dataset
uspto-grants-2008_10
Patent number
US07439237B2

Reaction notes

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