Sodium borohydride → HCID 68700870, compound

HRID 2244386Notes

Reaction equation

HRID 2244386 reaction equation
[NH2:1][C:2]1[CH:33]=[CH:32][C:31]([Cl:34])=[CH:30][C:3]=1[C:4]([N:6]([CH2:19][C:20]1[CH:25]=[CH:24][C:23]([C:26]([CH3:29])([CH3:28])[CH3:27])=[CH:22][CH:21]=1)[CH2:7][CH2:8][C:9]1[CH:14]=[CH:13][CH:12]=[C:11]([C:15]([F:18])([F:17])[F:16])[CH:10]=1)=[O:5].[CH2:35]([O:37][C:38](=[O:43])[CH:39](C=O)[CH3:40])[CH3:36].[BH4-].[Na+]>CCO>[CH2:35]([O:37][C:38](=[O:43])[CH2:39][CH2:40][NH:1][C:2]1[CH:33]=[CH:32][C:31]([Cl:34])=[CH:30][C:3]=1[C:4](=[O:5])[N:6]([CH2:19][C:20]1[CH:25]=[CH:24][C:23]([C:26]([CH3:29])([CH3:28])[CH3:27])=[CH:22][CH:21]=1)[CH2:7][CH2:8][C:9]1[CH:14]=[CH:13][CH:12]=[C:11]([C:15]([F:16])([F:17])[F:18])[CH:10]=1)[CH3:36].[C:26]([C:23]1[CH:24]=[CH:25][C:20]([CH2:19][N:6]([CH2:7][CH2:8][C:9]2[CH:14]=[CH:13][CH:12]=[C:11]([C:15]([F:16])([F:17])[F:18])[CH:10]=2)[C:4](=[O:5])[C:3]2[CH:30]=[C:31]([Cl:34])[CH:32]=[CH:33][C:2]=2[NH:1][CH2:40][CH2:39][CH2:38][OH:37])=[CH:21][CH:22]=1)([CH3:29])([CH3:28])[CH3:27]

Participants

6

Reactant 3

HCID 4311764Sodium borohydride2×HCID 10898741Ethyl 2-FormylpropionateHCID 68699354HCID 68699354, compound

Product 2

HCID 68696244HCID 68696244, compoundYield 7%HCID 68700870HCID 68700870, compoundYield 28%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A solution of 150 mg (0.31 mmol) of 2-amino-N-(4-tert-butyl-benzyl)-5-chloro-N-[2-(3-trifluoromethyl-phenyl)-ethyl]-benzamide and 76 mg (0.46 mmol) of formylpropionic acid ethylester (prepared by stirring 3,3-diethoxypropionic acid ethylester at RT with 1N—HCl followed by extraction with diethylether and concentration in vacuo) in 3 ml EtOH was refluxed for two hours. The reaction mixture was cooled down to RT and reacted with 17 mg (0.46 mmol) of sodium borohydride. After 5 min at RT and 30 min under reflux additional 9 mg (0.29 mmol) of sodium borohydride were added followed by 5 min at RT and 30 min under reflux. The reaction mixture was then concentrated, treated with diethylether and 2 drops 1N—HCl, and extracted twice with ethylacetate. The combined organic layers were washed with brine, dried over magnesium sulfate, filtered and concentrated in vacuo. The residue was purified by column chromatography (silica gel; heptane/EtOAc 90:10 to 50:50) to give 53 mg (28%) of 3-(2-{(4-tert-butyl-benzyl)-[2-(3-trifluoromethyl-phenyl)-ethyl]-carbamoyl}-4-chloro-phenylamino)-propionic acid ethyl ester as a light yellow viscous oil [MS (ISP) 489.4 (M+H)+] and 12 mg (7%) of N-(4-tert-butyl-benzyl)-5-chloro-2-(3-hydroxy-propylamino)-N-[2-(3-trifluoromethyl-phenyl)-ethyl]-benzamide as light yellow amorphous solid [MS (ISP) 547.4 (M+H)+]. A solution of 42 mg (0.07 mmol) of 3-(2-{(4-tert-butyl-benzyl)-[2-(3-trifluoromethyl-phenyl)-ethyl]-carbamoyl}-4-chloro-phenylamino)-propionic acid ethyl ester in 1 ml EtOH and 0.14 ml 1N-NaOH was stirred at 50° C. for 17 hours. The reaction mixture was concentrated in vacuo, treated with water and the pH was adjusted to 3 with 1N—HCl. The mixture was extracted twice with diethylether, washed with brine, dried over magnesium sulfate, filtered and concentrated in vacuo to give 39 mg (93%) of 3-(2-{(4-tert-butyl-benzyl)-[2-(3-trifluoromethyl-phenyl)-ethyl]-carbamoyl}-4-chloro-phenylamino)-propionic acid as an off-white foam. MS (ISP) 561.5 (M+H)+.

Workup

  1. additionwere added
  2. waitfollowed by 5 min at RT and 30 min
  3. temperatureunder reflux
  4. concentrationThe reaction mixture was then concentrated
  5. additiontreated with diethylether and 2 drops 1N—HCl
  6. extractionextracted twice with ethylacetate
  7. washThe combined organic layers were washed with brine
  8. dry with materialdried over magnesium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. customThe residue was purified by column chromatography (silica gel; heptane/EtOAc 90:10 to 50:50)

Sources & evidence

ORD record
ord-f198e2f1c9d34b0fa70f525083150345
Source dataset
uspto-grants-2010_03
Patent number
US07678818B2

Reaction notes

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