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

HRID 46020Notes

Reaction equation

HRID 46020 reaction equation
C[O:2][C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][CH:11]=1)[C@H:8]([C@H:12]([CH2:17][CH3:18])[C:13]([O:15][CH3:16])=[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]([C@H:12]([CH2:17][CH3:18])[C:13]([O:15][CH3:16])=[O:14])[CH2:7][CH2:6]2

Participants

5

Reactant 3

HCID 6343EthanethiolHCID 6451240Aluminum(III) ChlorideHCID 12132838HCID 12132838, compound

Product 1

HCID 11183909Methyl (2S)-2-[(1S)-5-hydroxy-2,3-dihydro-1H-inden-1-yl]butanoateYield 98.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a cold solution (ice water bath) of the compound prepared in Example 6 (233 g, 0.94 mol) in 2.5 L CH2Cl2, was added AlCl3 (630 g, 4.7 mol) slowly under Ar. The pot temperature was kept below 20° C., and the color of the reaction turned purple. EtSH (345 mL, 4.7 mol) was added slowly via an addition funnel to the reaction mixture, and the inside temperature was kept below 15° C. After 2 hours of stirring at below 20° C., the reaction went to completion by NMR analysis. The pot mixture was slowly poured into 2.5 L ice water with a strong agitation. The organic layer was separated, and the aqueous layer was extracted with 1 L CH2Cl2. The combined CH2Cl2 layers were washed with water (4×1 L) until pH 6.0-7.0, and then dried over Na2SO4. The product (216 g, 98%) was obtained as a white solid after solvent removal and vacuum drying. 1H NMR (DMSO-d6) δ 9.10 (s, 1H), 6.78 (d, 1H), 6.58 (d, 1H), 6.50 (dd, 1H), 3.60 (s, 3H), 3.20 (q, 1H), 2.70 (m, 2H), 2.40 (m, 1H), 2.08 (m, 1H), 1.80 (m, 1H), 1.50 (m, 2H), 0.80 (t, 3H).

Workup

  1. customwas kept below 20° C.
  2. customwas kept below 15° C
  3. customThe organic layer was separated
  4. extractionthe aqueous layer was extracted with 1 L CH2Cl2
  5. washThe combined CH2Cl2 layers were washed with water (4×1 L) until pH 6.0-7.0
  6. dry with materialdried over Na2SO4

Sources & evidence

ORD record
ord-873d9e02890d4106b73c4eac4638f3d8
Source dataset
uspto-grants-2013_09
Patent number
US08541618B2

Reaction notes

Loading…