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

HRID 962931

Reaction equation

HRID 962931 reaction equation
[C@@H:1]1(O)[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH2:3][C@H:2]1[OH:10].C(#[N:14])C.S(=O)(=O)(O)O.O1[C@@H]2CC3C([C@H]12)=CC=CC=3>O>[NH2:14][C@@H:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH2:3][C@@H:2]1[OH:10]

Participants

6

Reactant 4

HCID 1118Sulfuric AcidHCID 6342AcetonitrileHCID 247603trans-1,2-IndandiolHCID 1512567(1S,2R)-Indene oxide

Product 1

HCID 2725045(1R,2S)-(+)-cis-1-Amino-2-indanolYield 59.7%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

Into a 100 ml four-neck flask, 4.48 g (30.3 mmol) of trans-(±)-1,2-indandiol (II) and 40 ml of acetonitrile were introduced. This mixture was suspended. While this suspension was stirred at room temperature, 6.14 g (60.6 mmol) of 97% sulfuric acid was added thereto at room temperature in a period of 20 minutes. The temperature within the mixture increased from 19° C. to 35° C. The slurry was completely dissolved to form a slightly yellow transparent solution. The solution was stirred at 24° C. for 1 hour and then at 60° C. for 1 hour. An HPLC analysis of the contents revealed that 70.8% of cis-oxazoline derivative (IV: R=CH3) had been generated, while no trans-amide derivative (III': R=CH3, Y=OH) was detected. Then, 30 ml of water was added thereto and the resulting mixture was stirred at 60° C. for 3 hours. Acetonitrile was removed by azeotropic distillation. The remaining mixture was washed with dichloromethane and then subjected to liquid separation. When an aqueous solution of 25% sodium hydroxide was added to the water phase, a crystal deposited. This crystal was filtered off under reduced pressure, washed with water, and then dried to yield 2.70 g (yield: 59.7%) of cis-(±)-1-aminoindan-2-ol (V) as a white crystal. Its purity determined by an HPLC was 97.7%.

Workup

  1. temperatureThe temperature within the mixture increased from 19° C. to 35° C
  2. dissolutionThe slurry was completely dissolved
  3. customto form a slightly yellow transparent solution
  4. stirringThe solution was stirred at 24° C. for 1 hour
  5. waitat 60° C. for 1 hour
  6. stirringthe resulting mixture was stirred at 60° C. for 3 hours
  7. customAcetonitrile was removed by azeotropic distillation
  8. washThe remaining mixture was washed with dichloromethane
  9. customsubjected to liquid separation
  10. additionWhen an aqueous solution of 25% sodium hydroxide was added to the water phase
  11. filtrationThis crystal was filtered off under reduced pressure
  12. washwashed with water
  13. customdried

Sources & evidence

ORD record
ord-3ae3cf14fce747df8dbaa48e0ae20314
Source dataset
uspto-grants-1998_06
Patent number
US05760242

Linked notes

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