Lithium aluminum hydride → (8-Bromo-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulen-2-yl)-methanol

HRID 1848971Notes

Reaction equation

HRID 1848971 reaction equation
[AlH4-].[Li+].[Br:3][C:4]1[CH:20]=[CH:19][C:7]2[C:8]3[N:9]=[C:10]([C:16](O)=[O:17])[S:11][C:12]=3[CH2:13][CH2:14][O:15][C:6]=2[CH:5]=1>O1CCCC1>[Br:3][C:4]1[CH:20]=[CH:19][C:7]2[C:8]3[N:9]=[C:10]([CH2:16][OH:17])[S:11][C:12]=3[CH2:13][CH2:14][O:15][C:6]=2[CH:5]=1

Participants

4

Reactant 2

HCID 28112Lithium aluminum hydrideHCID 579001668-Bromo-4,5-dihydrobenzo[2,3]oxepino[4,5-d]thiazole-2-carboxylic acid

Product 1

HCID 58204050(8-Bromo-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulen-2-yl)-methanolYield 63.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

Lithium tetrahydroaluminate (0.363 g, 9.56 mmol) was suspended in tetrahydrofuran (30 mL) and cooled to 0° C. A solution of 8-Bromo-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulene-2-carboxylic acid (1.04 g, 3.19 mmol) in tetrahydrofuran (1 mL) was then added dropwise over a 10 min period. The resulting reaction mixture was stirred while warming to r.t. for 12 h. LCMS indicated that the reaction was completely converted with a minor uncharacterized impurity present (<5%). The reaction was quenched by diluting with saturated Rochelle's salt solution and EtOAc (1:1, 200 mL). The mixture was stirred very vigorously until the phases separated. The layers were then partitioned and the aqueous layer was extracted with EtOAc (3×). The combined organic portions were dried over MgSO4, filtered and concentrated. The crude residue was purified by ISCO chromatography (40 g column, 0-75% EtOAc/heptane) to provide 0.63 g (63% yield) of (8-Bromo-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulen-2-yl)-methanol. LC/MS (ESI+): m/z 313.2 (M+H).

Workup

  1. customThe resulting reaction mixture
  2. temperaturewhile warming to r.t. for 12 h
  3. customThe reaction was quenched
  4. additionby diluting with saturated Rochelle's salt solution and EtOAc (1:1, 200 mL)
  5. stirringThe mixture was stirred very vigorously until the phases
  6. customseparated
  7. customThe layers were then partitioned
  8. extractionthe aqueous layer was extracted with EtOAc (3×)
  9. dry with materialThe combined organic portions were dried over MgSO4
  10. filtrationfiltered
  11. concentrationconcentrated
  12. customThe crude residue was purified by ISCO chromatography (40 g column, 0-75% EtOAc/heptane)

Sources & evidence

ORD record
ord-23cc45d074724f59aba02e795345fcda
Source dataset
uspto-grants-2015_02
Patent number
US08952043B2

Reaction notes

Loading…