3-Chloro-4-fluoro-1-benzothiophene-2-carbonyl chloride → (3-Chloro-4-fluoro-benzo[b]thiophen-2-yl)methanol

HRID 2097046Notes

Reaction equation

HRID 2097046 reaction equation
[Cl:1][C:2]1[C:3]2[C:13]([F:14])=[CH:12][CH:11]=[CH:10][C:4]=2[S:5][C:6]=1[C:7](Cl)=[O:8].[H-].[Al+3].[Li+].[H-].[H-].[H-]>C1COCC1>[Cl:1][C:2]1[C:3]2[C:13]([F:14])=[CH:12][CH:11]=[CH:10][C:4]=2[S:5][C:6]=1[CH2:7][OH:8]

Participants

4

Reactant 2

HCID 125946453-Chloro-4-fluoro-1-benzothiophene-2-carbonyl chlorideHCID 21226445Aluminium lithium hydride

Product 1

HCID 59277586(3-Chloro-4-fluoro-benzo[b]thiophen-2-yl)methanolYield 96%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To an ice-cold suspension of 3-chloro-4-fluoro-benzo[b]thiophene-2-carbonyl chloride (5.46 g, 23.6 mmol) in THF (120 mL) was added lithium aluminum hydride (11.8 mL of a 1.0 M solution in THF, 11.8 mmol) dropwise. The mixture was stirred for 2 h then quenched with NaOH (0.35 N solution in H2O). The mixture was diluted with Et2O and the solution filtered. The filtrate was dried (Na2SO4) and concentrated. Purification by flash column chromatography (silica gel, hexanes/EtOAc, 8:2) gave the title compound (4.52 g, 96%) as an off-white solid: 1H NMR (300 MHz, CDCl3) δ 7.57 (d, J=8.1 Hz, 1H), 7.31 (ddd, J=8.0, 8.0, 4.7 Hz, 1H), 7.06 (dd, J=11.3, 8.0 Hz, 1H), 4.97 (d, J=6.2 Hz, 2H),

Workup

  1. customthen quenched with NaOH (0.35 N solution in H2O)
  2. additionThe mixture was diluted with Et2O
  3. filtrationthe solution filtered
  4. dry with materialThe filtrate was dried (Na2SO4)
  5. concentrationconcentrated
  6. customPurification by flash column chromatography (silica gel, hexanes/EtOAc, 8:2)

Sources & evidence

ORD record
ord-722b2b2194e34cb480deca79916359a7
Source dataset
uspto-grants-2013_05
Patent number
US08450307B2

Reaction notes

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