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

HRID 1362300Notes

Reaction equation

HRID 1362300 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), 2.04 (t, J=6.2 Hz, 1H).

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-662f2cb93f7d44c98c3f08d7f6255b00
Source dataset
uspto-grants-2011_02
Patent number
US07879872B2

Reaction notes

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