1,2-Dichloroethane → HCID 86622846, compound

HRID 551050Notes

Reaction equation

HRID 551050 reaction equation
[NH2:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]2[C:3]=1[CH:4]([CH2:19][CH2:20][CH2:21][C:22]([O-:24])=O)[CH2:5][N:6]2[CH2:11][C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13].[Li+].C(Cl)CCl.C1C=NC2N(O)N=NC=2C=1.C(N(CC)C(C)C)(C)C>CN(C=O)C>[O:24]=[C:22]1[NH:1][C:2]2[C:3]3[CH:4]([CH2:5][N:6]([CH2:11][C:12]([O:14][C:15]([CH3:16])([CH3:17])[CH3:18])=[O:13])[C:7]=3[CH:8]=[CH:9][CH:10]=2)[CH2:19][CH2:20][CH2:21]1

Participants

6

Reactant 4

HCID 111,2-DichloroethaneHCID 81531DiisopropylethylamineHCID 181649HOAtHCID 66636701HCID 66636701, compound

Product 1

HCID 86622846HCID 86622846, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of lithium 4-[4-amino-1-(2-tert-butoxy-2-oxoethyl)-2,3-dihydro-1H-indol-3-yl]butanoate from Step E (900 mg, 2.69 mmol), EDC (1.29 g, 6.73 mmol), HOAT (916 mg, 6.73 mmol), and N,N-diisopropylethylamine (0.94 mL, 5.38 mmol) was stirred in DMF (10 mL) at ambient temperature for 4 h, then concentrated under reduced pressure. The residue was partitioned between saturated aqueous NaHCO3 (5 mL) and EtOAc (50 mL). The organic layer was washed with H2O (5 mL), then 10% aqueous citric acid (5 mL), then dried over Na2SO4, filtered, and concentrated in vacuo. The crude product was purified by silica gel chromatography, eluting with a gradient of hexane:EtOAc—80:20 to 0:100, to give the racemic product. The enantiomers were resolved by HPLC, utilizing a Chiralpak AS column and eluting with CH3CN:MeOH—25:75. The first major peak to elute was tert-butyl (6-oxo-2a,3,4,5,6,7-hexahydroazocino[4,3,2-cd]indol-1 (2H)-yl)acetate, enantiomer A, the title compound, and the second major peak to elute was tert-butyl (6-oxo-2a,3,4,5,6,7-hexahydroazocino[4,3,2-cd]indol-1(2H)-yl)acetate, enantiomer B. MS: m/z=317 (M+1).

Workup

  1. concentrationconcentrated under reduced pressure
  2. customThe residue was partitioned between saturated aqueous NaHCO3 (5 mL) and EtOAc (50 mL)
  3. washThe organic layer was washed with H2O (5 mL)
  4. dry with material10% aqueous citric acid (5 mL), then dried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe crude product was purified by silica gel chromatography
  8. washeluting with a gradient of hexane
  9. customEtOAc—80:20 to 0:100, to give the racemic product
  10. washeluting with CH3CN
  11. washThe first major peak to elute
  12. washthe title compound, and the second major peak to elute

Sources & evidence

ORD record
ord-d9b41b5679c34073ba1e1ce1eea35e45
Source dataset
uspto-grants-2011_05
Patent number
US07947677B2

Reaction notes

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