Ethanol → HCID 71270610, compound

HRID 2406262Notes

Reaction equation

HRID 2406262 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[C@@H:7]([N:11]1C(=O)C3C(=CC=CC=3)C1=O)[C@@H:6]([O:22][CH3:23])[CH2:5]2.C(O)C.NN>>[Cl:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[C@@H:7]([NH2:11])[C@@H:6]([O:22][CH3:23])[CH2:5]2

Participants

4

Reactant 3

HCID 702EthanolHCID 9321HydrazineHCID 71270656HCID 71270656, compound

Product 1

HCID 71270610HCID 71270610, compoundYield 99.6%

Conditions

Temperature
90 °C

Procedure

To a suspension of 2-[(1R,2S)-5-chloro-2-methoxy-2,3-dihydro-1H-inden-1-yl]-1H-isoindole-1,3(2H)-dione (7) (25.8 g, 0.0787 mol) in ethanol (260 mL, 4.4 mol) was added hydrazine (4.94 mL, 0.157 mol), and the flask was affixed with a reflux condenser and heated to a bath temperature of 90° C. A precipitate began to form after several minutes of stirring and after 1 hour of heating the mixture had become a thick slurry/solid. The reaction was cooled to room temperature and the solid reaction byproducts were filtered and washed with CH2Cl2 (˜300 mL). The volatiles were removed from the filtrate in vacuo, and the residue was suspended in CH2Cl2 (250 mL), at which point the solid byproducts were again removed by filtration. The volatiles were removed in vacuo, and the residue was again suspended in CH2Cl2 (˜50 mL). The solid byproducts were removed a final time by filtration to afford (1R,2S)-5-chloro-2-methoxyindan-1-amine (15.5 g, 99%) as a red/orange waxy solid. LCMS: (FA) ES+ molecular ion 198, major ionization 181; 1H NMR (400 MHz, DMSO) δ 7.30 (d, J=7.9, 1H), 7.25-7.16 (m, 2H), 4.14 (d, J=4.9, 1H), 3.89 (td, J=2.8, 4.9, 1H), 3.29 (s, 3H), 2.89 (ddd, J=3.8, 16.4, 21.3, 2H), 2.04 (s, 2H). Chiral HPLC (Chiralpak AD 4.6×250 column eluted with 95/5/0.1% hexane/EtOH/DEA @ 1.0 ml/min-30 min run) showed an ee of >99%.

Workup

  1. customthe flask was affixed with a reflux condenser
  2. customto form after several minutes
  3. temperatureof heating the mixture
  4. temperatureThe reaction was cooled to room temperature
  5. customthe solid reaction byproducts
  6. filtrationwere filtered
  7. washwashed with CH2Cl2 (˜300 mL)
  8. customThe volatiles were removed from the filtrate in vacuo
  9. customwere again removed by filtration
  10. customThe volatiles were removed in vacuo
  11. customThe solid byproducts were removed a final time
  12. filtrationby filtration

Sources & evidence

ORD record
ord-63b82baffa98443181f6591eaf3958ab
Source dataset
uspto-grants-2014_08
Patent number
US08809356B2

Reaction notes

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