Sulfuric Acid → (1R,2S)-(+)-cis-1-Amino-2-indanol

HRID 962929Notes

Reaction equation

HRID 962929 reaction equation
[O:1]1[C@@H:3]2[CH2:4][C:5]3[C:10]([C@H:2]12)=[CH:9][CH:8]=[CH:7][CH:6]=3.C(#[N:13])C.ClCCl.S(=O)(=O)(O)O>O>[NH2:13][C@@H:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH2:4][C@@H:3]1[OH:1]

Participants

6

Reactant 4

HCID 1118Sulfuric AcidHCID 6342AcetonitrileHCID 6344DichloromethaneHCID 1512567(1S,2R)-Indene oxide2×

Product 1

HCID 2725045(1R,2S)-(+)-cis-1-Amino-2-indanolYield 66.8%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
-30 °C

Procedure

Into a 300 ml four-neck flask, 10.0 g (75.8 mmol) of cis-(±)-1,2-epoxyindan (VI), 50 ml of acetonitrile, and 40 ml of dichloromethane were introduced. This mixture was cooled to -30° C. in a dry ice/acetone bath. To this mixture, 11.14 g (113.6 mmol) of 100% sulfuric acid (prepared from 97% sulfuric acid and fuming sulfuric acid) was dropwise added at -30° to -27° C. in a period of 1 hour. When left for 1 hour to return to room temperature, the mixture became white and turbid to form a slurry. An HPLC analysis of the contents revealed that 46.8% of cis-oxazoline derivative (IV: R=CH3) had been generated. No cis-amide derivative (III: R=CH3) was detected. As the mixture was heated while 72 ml of water being added thereto, 100 ml of an azeotrope of acetonitrile/dichloromethane/water was distilled off in a period of 1 hour. The remaining mixture was cooled to room temperature, washed twice with 100 ml of dichloromethane, and then subjected to liquid separation. The water phase was adjusted to a strongly alkali state by an addition of 25% sodium hydroxide. The crystal deposited thereby was filtered off under reduced pressure, washed with water, and then dried to yield 7.53 g (yield: 66.8%) of cis-(±)-1-aminoindan-2-ol (V) as a white crystal. Its purity determined by an HPLC was 95.5%.

Workup

  1. customto return to room temperature
  2. customto form a slurry
  3. additionadded
  4. distillation100 ml of an azeotrope of acetonitrile/dichloromethane/water was distilled off in a period of 1 hour
  5. temperatureThe remaining mixture was cooled to room temperature
  6. washwashed twice with 100 ml of dichloromethane
  7. customsubjected to liquid separation
  8. additionThe water phase was adjusted to a strongly alkali state by an addition of 25% sodium hydroxide
  9. filtrationThe crystal deposited thereby was filtered off under reduced pressure
  10. washwashed with water
  11. customdried

Sources & evidence

ORD record
ord-86d50633fa3144a29d51348676f52ed9
Source dataset
uspto-grants-1998_06
Patent number
US05760242

Reaction notes

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