3-Bromooxan-2-one → 4-(6,7-dihydro-5H-pyrano[2,3-d][1,3]thiazol-2-yl)-2-propylphenol

HRID 603512Notes

Reaction equation

HRID 603512 reaction equation
Br[CH:2]1[CH2:8][CH2:7][CH2:6][O:5][C:3]1=O.[OH:9][C:10]1[CH:15]=[CH:14][C:13]([C:16](=[S:18])[NH2:17])=[CH:12][C:11]=1[CH2:19][CH2:20][CH3:21]>C(O)C>[S:18]1[C:2]2[CH2:8][CH2:7][CH2:6][O:5][C:3]=2[N:17]=[C:16]1[C:13]1[CH:14]=[CH:15][C:10]([OH:9])=[C:11]([CH2:19][CH2:20][CH3:21])[CH:12]=1

Participants

4

Reactant 2

HCID 110629723-Bromooxan-2-oneHCID 1359745034-Hydroxy-3-propylbenzenecarbothioamide

Product 1

HCID 1363400774-(6,7-dihydro-5H-pyrano[2,3-d][1,3]thiazol-2-yl)-2-propylphenolYield 62.7%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A stirred mixture of α-bromo-δ-valerolactone (77% pure; 300 g, 1.3 mol), 4-hydroxy-3-propylbenzenecarbothioamide (229.09 g; 1.2 mol) (Example 504), and absolute ethanol (2.5 L) was gradually heated under nitrogen. A significant gas evolution occurred. When the latter had slowed, the mixture was brought to reflux. After 16 h at reflux, the mixture was cooled to rt, and then concentrated in vacuo. The residue was taken-up in 50% dichloromethane/hexanes, filtered, and the solid triturated and washed with more of the solvent mixture (700 mL total). After washing with hexanes and drying in vacuo, 207.1 g (58%) of the title compound were obtained as a yellow solid. The filtrate was concentrated in vacuo, and the residue chromatographed on silica gel to afford a thick oil containing impure product in which crystals formed. Filtration, trituration, and washing of the solid with ethanol afforded 27.6 g (234.7 g total; 66.1% yield) of opaque, pastel orange crystals, mp 152-154° C.; 1H NMR (DMSO-d6): δ 9.86 (broad exchangeable s, 1H), 7.5 (d, 1H), 7.4 (dd, 1H), 6.8 (d, 1H), 4.2 (t, 2H), 2.7 (t, 2H), 2.5 (t, 2H), 2.0 (m, 2H), 1.5 (m, 2H), 0.9 (t, 3H); LCMS: RT=3.0 min, (M+H)+ 276.

Workup

  1. temperaturewas gradually heated under nitrogen
  2. temperatureto reflux
  3. temperatureAfter 16 h at reflux
  4. concentrationconcentrated in vacuo
  5. filtrationfiltered
  6. customthe solid triturated
  7. washwashed with more of the solvent mixture (700 mL total)
  8. washAfter washing with hexanes
  9. customdrying in vacuo

Sources & evidence

ORD record
ord-ec1c68cdcdd54c0abeda9d05e9985369
Source dataset
uspto-grants-2011_03
Patent number
US07906653B2

Reaction notes

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