Hydrochloric Acid → (S)-3,3-Dimethyl-2,3-dihydro-1H-inden-1-amine

HRID 222188Notes

Reaction equation

HRID 222188 reaction equation
[CH3:1][C:2]1([CH3:21])[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[C@@H:4]([NH:11][C@H](C2C=CC=CC=2)CO)[CH2:3]1.C([O-])(=O)C.C([O-])(=O)C.C([O-])(=O)C.C([O-])(=O)C.[Pb+4].Cl>CO>[CH3:1][C:2]1([CH3:21])[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[C@@H:4]([NH2:11])[CH2:3]1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 66618252(R)-2-(((S)-3,3-Dimethyl-2,3-dihydro-1H-inden-1-yl)amino)-2-phenylethanolHCID 178418268HCID 178418268, compound

Product 1

HCID 57572827(S)-3,3-Dimethyl-2,3-dihydro-1H-inden-1-amineYield 51%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent2×

Procedure

A solution of (2R)-2-{[(1S)-3,3-dimethyl-2,3-dihydro-1H-inden-1-yl]amino}-2-phenylethanol (1.44 g, 5.13 mmol) in MeOH (40.0 mL) was added to a stirred solution of lead tetraacetate (3.75 g, 8.03 mmol) in MeOH (60.0 mL) at 0° C. dropwise over 20 min. After stirring for 45 min, the reaction was quenched via addition of a 10% solution of sodium carbonate in water (76.0 mL) and the mixture was stirred for 10 min. DCM (200 mL) was then added and the layers were separated. The aqueous layer was extracted with DCM (50.0 mL). The combined organic layers were concentrated in vacuo and the residue was dissolved in ethanol (190 mL) and treated with a 10.4 M aqueous solution of hydrochloric acid (5.70 mL, 59.3 mmol). The resulting mixture was then heated to reflux for 16 h. The cooled reaction was concentrated in vacuo and partitioned between water (150 mL) and diethyl ether (50.0 mL). The aqueous layer was adjusted to pH 10 via addition of sodium carbonate and extracted with diethyl ether (3×50.0 mL). The combined organic layers were concentrated in vacuo and silica gel chromatography eluting with a gradient of 0 to 10% MeOH in DCM to afford the title compound as a pale yellow oil (420 mg, 51%). 1H NMR (CD3OD, 300 MHz, δ): 7.34-7.14 (m, 4H), 4.45-4.37 (m, 1H), 2.38 (dd, J=7.1, 12.4 Hz, 1H), 1.73 (br s, 2H), 1.60 (dd, J=8.7, 12.4 Hz, 1H), 1.39 (s, 3H), 1.19 (s, 3H) ppm.

Workup

  1. customthe reaction was quenched via addition of a 10% solution of sodium carbonate in water (76.0 mL)
  2. stirringthe mixture was stirred for 10 min
  3. additionDCM (200 mL) was then added
  4. customthe layers were separated
  5. extractionThe aqueous layer was extracted with DCM (50.0 mL)
  6. concentrationThe combined organic layers were concentrated in vacuo
  7. dissolutionthe residue was dissolved in ethanol (190 mL)
  8. temperatureThe resulting mixture was then heated
  9. temperatureto reflux for 16 h
  10. customThe cooled reaction
  11. concentrationwas concentrated in vacuo
  12. custompartitioned between water (150 mL) and diethyl ether (50.0 mL)
  13. additionThe aqueous layer was adjusted to pH 10 via addition of sodium carbonate
  14. extractionextracted with diethyl ether (3×50.0 mL)
  15. concentrationThe combined organic layers were concentrated in vacuo and silica gel chromatography
  16. washeluting with a gradient of 0 to 10% MeOH in DCM

Sources & evidence

ORD record
ord-045df3191a7d47b4b1e0faf437691cce
Source dataset
uspto-grants-2012_06
Patent number
US08207177B2

Reaction notes

Loading…