Triethylamine → N-((1S,2R,4R)-4-(isopropyl(methyl)amino)-2-(phenylsulfonylmethyl)cyclohexyl)-4-oxo-4-(3-(trifluoromethyl)phenyl)butanamide

HRID 641595Notes

Reaction equation

HRID 641595 reaction equation
[O:1]=[C:2]([C:8]1[CH:13]=[CH:12][CH:11]=[C:10]([C:14]([F:17])([F:16])[F:15])[CH:9]=1)[CH2:3][CH2:4][C:5]([OH:7])=O.C(N(CC)CC)C.ClC(OCC(C)C)=O.[CH:33]([N:36]([CH3:54])[C@@H:37]1[CH2:42][CH2:41][C@H:40]([NH2:43])[C@H:39]([CH2:44][S:45]([C:48]2[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=2)(=[O:47])=[O:46])[CH2:38]1)([CH3:35])[CH3:34].[OH-].[Na+]>C1COCC1>[CH:33]([N:36]([CH3:54])[C@@H:37]1[CH2:42][CH2:41][C@H:40]([NH:43][C:5](=[O:7])[CH2:4][CH2:3][C:2](=[O:1])[C:8]2[CH:13]=[CH:12][CH:11]=[C:10]([C:14]([F:17])([F:16])[F:15])[CH:9]=2)[C@H:39]([CH2:44][S:45]([C:48]2[CH:49]=[CH:50][CH:51]=[CH:52][CH:53]=2)(=[O:46])=[O:47])[CH2:38]1)([CH3:35])[CH3:34]

Participants

7

Reactant 5

HCID 8471TriethylamineHCID 14798Sodium HydroxideHCID 62365Isobutyl chloroformateHCID 134088364-Oxo-4-(3-trifluoromethylphenyl)butyric acidHCID 68468828(1R*,3R*,4S*)-N1-isopropyl-N1-methyl-3-(phenylsulfonylmethyl)cyclohexane-1,4-diamine

Product 1

HCID 11249846N-((1S,2R,4R)-4-(isopropyl(methyl)amino)-2-(phenylsulfonylmethyl)cyclohexyl)-4-oxo-4-(3-(trifluoromethyl)phenyl)butanamideYield 62.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

Commercially available 4-oxo-4-(3-trifluoromethylphenyl)butyric acid (45.5 mg, 0.185 mmol) was dissolved in dry THF (3 mL). To the above solution was added triethyl amine (18.7 mg, 0.185 mmol) and isobutyl chloroformate (25.3 mg, 0.185 mmol) at 0° C. The mixture was stirred at 0° C. for 5 min. before the solution of (1R,3R,4S)-N1-isopropyl-N1-methyl-3-(phenylsulfonylmethyl)cyclohexane-1,4-diamine (see 30b) (50 mg, 0.154 mmol) in dry THF (3 mL) was added. The resulting mixture was warmed up to room temperature. The reaction was completed by 0.5 h. The mixture was treated with 1 N NaOH (5 mL) and extracted with CH2Cl2 (10 mL×2). The organic extracts were washed with water, brine and evaporated. The residue was chromatographed on silica gel (4% NH4OH/MeOH/CH2Cl2) to give the product (53 mg). MS found: (M+1)+: 553.32

Workup

  1. additionwas added
  2. extractionextracted with CH2Cl2 (10 mL×2)
  3. washThe organic extracts were washed with water, brine
  4. customevaporated
  5. customThe residue was chromatographed on silica gel (4% NH4OH/MeOH/CH2Cl2)

Sources & evidence

ORD record
ord-af5ac32a435644dbad7cfa4fe6bf833e
Source dataset
uspto-grants-2010_04
Patent number
US07696205B2

Reaction notes

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