Acetic Acid → 8-Bromo-1,2,3,4-tetrahydronaphthalen-2-one

HRID 2210922Notes

Reaction equation

HRID 2210922 reaction equation
Br[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[CH2:8][C:9](Cl)=O.[Br:12][C:13]1[CH:14]=[CH:15][CH:16]=[C:17]2[C:22]=1[CH2:21][C:20](=[O:23])[CH2:19][CH2:18]2.C(O)(=O)C.C([BH3-])#[N:29].[Na+]>CO.C1COCC1>[Br:12][C:13]1[CH:14]=[CH:15][CH:16]=[C:17]2[C:22]=1[CH2:21][C:20](=[O:23])[CH2:19][CH2:18]2.[Br:12][C:13]1[CH:14]=[CH:15][CH:16]=[C:17]2[C:22]=1[CH2:21][CH:20]([NH:29][C@@H:8]([CH3:9])[C:3]1[CH:4]=[CH:5][CH:6]=[CH:7][CH:2]=1)[CH2:19][CH2:18]2

Participants

8

Reactant 4

HCID 176Acetic AcidHCID 41361878-Bromo-1,2,3,4-tetrahydronaphthalen-2-oneHCID 41383862-Bromophenylacetyl chlorideHCID 5003444Sodium cyanoborohydride

Product 2

HCID 41361878-Bromo-1,2,3,4-tetrahydronaphthalen-2-oneHCID 228505508-bromo-N-[(S)-alpha-methylbenzyl]-2-aminotetralin

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

Initially, 8-Bromo-2-tetralone was prepared by substituting 2-bromophenylacetylchloride in the procedure described in A. H. Horn, C. J. Grol, D. Dijkstra, A. H. Mulder, J. Med. Chem. 21,825 (1978). Next, 8-bromo-2-tetralone (25 g, 111.1 mmol), S-(-)-alpha-methylbenzylamine (71.5 ml, 5 eq.), acetic acid (80 ml), 4 A molecular sieves (15 ml), THF (125 ml) and methanol (125 ml) were introduced into a flask and cooled to 0°. Sodium cyanoborohydride (1.5 g, 2 eq.) was added in portions over a 15 min period. The slurry was allowed to stir for 3 hr. The slurry was filtered and the solvent reduced to a syrup by evaporation in vacuo. The residue was partitioned between ether and 2N aqueous sodium hydroxide. The ether layer was washed with water (3×) and brine. After drying over anhydrous sodium sulfate the solvent was removed in vacuo. The viscous oil was placed on a flash silica gel column (5 cm×50 cm) and eluted with ethyl acetate/hexane (8%) to separate the higher Rf (+)-diastereomer (solidifies upon standing, 17 g). The solvent was raised to 12% to elute the lower Rf (-)-diastereomer (an oil, 16 g). In this manner the 8-bromo-N-[(S)-alpha-methylbenzyl]-2-aminotetralin was obtained.

Workup

  1. temperaturecooled to 0°
  2. filtrationThe slurry was filtered
  3. customthe solvent reduced to a syrup by evaporation in vacuo
  4. customThe residue was partitioned between ether and 2N aqueous sodium hydroxide
  5. washThe ether layer was washed with water (3×) and brine
  6. dry with materialAfter drying over anhydrous sodium sulfate the solvent
  7. customwas removed in vacuo
  8. washeluted with ethyl acetate/hexane (8%)
  9. customto separate the higher Rf (+)-diastereomer (solidifies upon standing, 17 g)
  10. temperatureThe solvent was raised to 12%
  11. washto elute the lower Rf (-)-diastereomer (an oil, 16 g)

Sources & evidence

ORD record
ord-d29c53a129a54021a01ab4e93495163d
Source dataset
uspto-grants-1995_10
Patent number
US05461061

Reaction notes

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