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

HRID 603366Notes

Reaction equation

HRID 603366 reaction equation
C[O:2][C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][CH:11]=1)[C@H:8]([CH2:12][C:13]([O:15][CH2:16][CH3:17])=[O:14])[CH2:7][CH2:6]2.[Al+3].[Cl-].[Cl-].[Cl-].CCS>C(Cl)Cl>[OH:2][C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][CH:11]=1)[C@H:8]([CH2:12][C:13]([O:15][CH2:16][CH3:17])=[O:14])[CH2:7][CH2:6]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) δ 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 (Cl) 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-afe8b417a7a44c78b4522ae0f6a0901d
Source dataset
uspto-grants-2011_03
Patent number
US07906653B2

Reaction notes

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