Ethanethiol → ethyl 2-[(1S)-5-hydroxy-2,3-dihydro-1H-inden-1-yl]acetate

HRID 2235837Notes

Reaction equation

HRID 2235837 reaction equation
[CH2:1]([O:3][C:4](=[O:17])[CH2:5][C@H:6]1[C:14]2[C:9](=[CH:10][C:11]([O:15]C)=[CH:12][CH:13]=2)[CH2:8][CH2:7]1)[CH3:2].[Al+3].[Cl-].[Cl-].[Cl-].CCS>C(Cl)Cl>[CH2:1]([O:3][C:4](=[O:17])[CH2:5][C@H:6]1[C:14]2[C:9](=[CH:10][C:11]([OH:15])=[CH:12][CH:13]=2)[CH2:8][CH2:7]1)[CH3:2]

Participants

5

Reactant 3

HCID 6343EthanethiolHCID 6451240Aluminum(III) ChlorideHCID 16110496Ethyl [(1S)-5-methoxy-2,3-dihydro-1H-inden-1-yl]acetate

Product 1

HCID 16110404ethyl 2-[(1S)-5-hydroxy-2,3-dihydro-1H-inden-1-yl]acetateYield 96.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a cold solution (ice water bath) of the compound (346 g, 1.48 mol) prepared in Example 5 in CH2Cl2 (4.2 L), was added AlCl3 (984.6 g, 7.38 mol) portionwise under argon such that the reaction temperature was maintained below 10° C. The light brown suspension was stirred for 10 min, then EtSH (546 mL, 7.38 mol) was added dropwise at such a rate that the reaction temperature was maintained below 5° C. After 2.5 h of stirring below 10° C., the reaction mixture was slowly poured into 6 L ice water with strong agitation. The organic layer was separated, and the aqueous layer was extracted with CH2Cl2 (3×1 L). The combined CH2Cl2 layers were washed with water (2×1 L), then dried over Na2SO4. The solvent was removed under reduced pressure, giving a brown oil, which was filtered through a pad of silica gel (eluted with 0-10% EtOAc/Hexanes). Fractions were collected, and the title compound (314 g, 96%) was obtained as a thick yellow oil after solvent removal and vacuum drying. 1H NMR (CDCl3) 6.92 (d, 1H), 6.62 (d, 1H), 6.55 (dd, 1H), 4.10 (q, 2H), 3.43 (q, 1H), 2.75 (m, 2H), 2.64 (dd, 1H), 2.31 (dd, 1H), 2.29 (m, 1H), 1.67 (m, 1H), 1.20 (t, 3H). MS (CI) m/z 221 [M+H]+.

Workup

  1. temperaturewas maintained below 10° C
  2. temperaturewas maintained below 5° C
  3. stirringAfter 2.5 h of stirring below 10° C.
  4. customThe organic layer was separated
  5. extractionthe aqueous layer was extracted with CH2Cl2 (3×1 L)
  6. washThe combined CH2Cl2 layers were washed with water (2×1 L)
  7. dry with materialdried over Na2SO4
  8. customThe solvent was removed under reduced pressure
  9. customgiving a brown oil, which
  10. filtrationwas filtered through a pad of silica gel (eluted with 0-10% EtOAc/Hexanes)
  11. customFractions were collected

Sources & evidence

ORD record
ord-d26b4a335c3a42829ab6e2f6db8c39a0
Source dataset
uspto-grants-2010_05
Patent number
US07714004B2

Reaction notes

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