1,2-Dichloroethane → HCID 178450646, compound

HRID 1717700Notes

Reaction equation

HRID 1717700 reaction equation
[C:1]([C@H:5]1[CH2:10][CH2:9][C@H:8]([NH:11][CH:12]2[C:20]3[C:15](=[CH:16][C:17]([C:21]([O:23][CH2:24][CH2:25][CH2:26][CH3:27])=[O:22])=[CH:18][CH:19]=3)[CH2:14][CH2:13]2)[CH2:7][CH2:6]1)([CH3:4])([CH3:3])[CH3:2].[F:28][C:29]([F:42])([F:41])[O:30][C:31]1[CH:36]=[CH:35][C:34]([CH2:37][C:38](O)=[O:39])=[CH:33][CH:32]=1.C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1.CCN(C(C)C)C(C)C.C([O-])(O)=O.[Na+]>CN(C=O)C.CCCCCC.CCOC(C)=O>[C:1]([C@H:5]1[CH2:10][CH2:9][C@H:8]([N:11]([C:38](=[O:39])[CH2:37][C:34]2[CH:35]=[CH:36][C:31]([O:30][C:29]([F:41])([F:28])[F:42])=[CH:32][CH:33]=2)[CH:12]2[C:20]3[C:15](=[CH:16][C:17]([C:21]([O:23][CH2:24][CH2:25][CH2:26][CH3:27])=[O:22])=[CH:18][CH:19]=3)[CH2:14][CH2:13]2)[CH2:7][CH2:6]1)([CH3:4])([CH3:3])[CH3:2]

Participants

10

Reactant 6

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 27773192-[4-(Trifluoromethoxy)phenyl]acetic acidHCID 178450643HCID 178450643, compound

Product 1

HCID 178450646HCID 178450646, compoundYield 84%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 8058HexaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of butyl 1-[(trans-4-tert-butylcyclohexyl)amino]indane-5-carboxylate (0.30 g, 0.81 mmol) in DMF/CH2CL2 (1:1, 10 mL) was added [4-(trifluoromethoxy)phenyl]acetic acid (0.21 g, 0.97 mmol), EDC (0.20 g, 1.05 mmol), HOBt (0.11 g, 0.81 mmol) and DIEA (0.45 mL, 2.43 mmol). After stirring at room temperature for 18 h, the reaction mixture was poured into saturated aqueous NaHCO3 (20 mL) and extracted with EtOAc (30 mL). The organic layer was washed with brine (2×10 mL), dried over Na2SO4, filtered and concentrated. Chromatography (10% to 20% EtOAc in Hexane) gave 0.39 g (84% yield) of butyl 1-((trans-4-tert-butylcyclohexyl){[4-(trifluoromethoxy)phenyl]acetyl}amino)indane-5-carboxylate. HPLC/MS: m/z=574.2 (M+1), Rt=3.19 min. The racemic compound was then resolved on chiral HPLC (ChiralPak AD column, 5% EtOH in n-Heptane) to give enantiomer A (+) (Rt=8.65 min) and B (−) (Rt=12.0 min).

Workup

  1. extractionextracted with EtOAc (30 mL)
  2. washThe organic layer was washed with brine (2×10 mL)
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-abc90c9a6f0d49fe8a54553bdf03c0b1
Source dataset
uspto-grants-2010_09
Patent number
US07803951B2

Reaction notes

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