HCID 86674082, compound → HCID 71059430, compound

HRID 921023Notes

Reaction equation

HRID 921023 reaction equation
[NH2:1][C:2]1[CH:7]=[C:6]([Br:8])[CH:5]=[CH:4][C:3]=1[NH:9][C:10]([C@@H:12]1[CH2:20][C@H:19]2[C@H:14]([CH2:15][CH2:16][CH2:17][CH2:18]2)[N:13]1[C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])=O.NC1C=CC(Br)=CC=1NC([C@@H]1C[C@H]2[C@H](CCCC2)N1C(OC(C)(C)C)=O)=O>C(O)(=O)C>[Br:8][C:6]1[CH:5]=[CH:4][C:3]2[N:9]=[C:10]([C@@H:12]3[CH2:20][C@H:19]4[C@H:14]([CH2:15][CH2:16][CH2:17][CH2:18]4)[N:13]3[C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[NH:1][C:2]=2[CH:7]=1

Participants

4

Reactant 2

HCID 86674082HCID 86674082, compoundHCID 86674083HCID 86674083, compound

Product 1

HCID 71059430HCID 71059430, compound

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Conditions

Temperature
65 °C

Procedure

An isomeric mixture (14) of (2S,3aS,7aS)-tert-butyl 2-((2-amino-4-bromophenyl)carbamoyl)octahydro-1H-indole-1-carboxylate and (2S,3aS,7aS)-tert-butyl 2-((2-amino-5-bromophenyl)carbamoyl)octahydro-1H-indole-1-carboxylate (160 g, 0.36 mol) was dissolved in acetic acid (480 mL) and the reaction mixture was stirred at 65° C. until the starting materials were consumed (as judged by LC-MS analysis). The reaction was cooled to rt and the solvent was removed under vacuum. The remaining residue was dissolved in ethyl acetate (500 mL) and aq ammonia (100 mL) was added carefully. Additional water (100 mL) was added and the organic layer was separated and collected. The aq phase was extracted with ethyl acetate (2×300 mL). The combined organic phase was washed with water (200 mL), followed by brine (200 mL), and dried over MgSO4. The solution was concentrated and the remaining residue was purified by silica gel column chromatography (hexanes/ethyl acetate) to afford (2S,3aS,7aS)-tert-butyl 2-(6-bromo-1H-benzo[d]imidazol-2-yl)octahydro-1H-indole-1-carboxylate (15) (140 g).

Workup

  1. customwere consumed (as judged by LC-MS analysis)
  2. temperatureThe reaction was cooled to rt
  3. customthe solvent was removed under vacuum
  4. dissolutionThe remaining residue was dissolved in ethyl acetate (500 mL)
  5. additionaq ammonia (100 mL) was added carefully
  6. additionAdditional water (100 mL) was added
  7. customthe organic layer was separated
  8. customcollected
  9. extractionThe aq phase was extracted with ethyl acetate (2×300 mL)
  10. washThe combined organic phase was washed with water (200 mL)
  11. dry with materialdried over MgSO4
  12. concentrationThe solution was concentrated
  13. customthe remaining residue was purified by silica gel column chromatography (hexanes/ethyl acetate)

Sources & evidence

ORD record
ord-9a78adf2618a4959b7edca38a60afc22
Source dataset
uspto-grants-2016_03
Patent number
US09273082B2

Reaction notes

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