3-Chloro-5-fluorobenzo[b]thiophene-2-carbonyl chloride → (3-Chloro-7-fluoro-benzo[b]thiophen-2-yl)methanol

HRID 2097050Notes

Reaction equation

HRID 2097050 reaction equation
ClC1C2C=C(F)C=CC=2SC=1C(Cl)=O.[Cl:15][C:16]1[C:17]2[CH:27]=[CH:26][CH:25]=[C:24]([F:28])[C:18]=2[S:19][C:20]=1[C:21](Cl)=[O:22].[H-].[Al+3].[Li+].[H-].[H-].[H-]>C1COCC1>[Cl:15][C:16]1[C:17]2[CH:27]=[CH:26][CH:25]=[C:24]([F:28])[C:18]=2[S:19][C:20]=1[CH2:21][OH:22]

Participants

5

Reactant 3

HCID 148724863-Chloro-5-fluorobenzo[b]thiophene-2-carbonyl chlorideHCID 21226445Aluminium lithium hydrideHCID 592776183-Chloro-7-fluoro-benzo[b]thiophene-2-carbonyl chloride

Product 1

HCID 59277539(3-Chloro-7-fluoro-benzo[b]thiophen-2-yl)methanolYield 11.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To an ice-cold suspension of a 6:1 mixture of 3-chloro-5-fluoro-benzo[b]thiophene-2-carbonyl chloride and 3-chloro-7-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 4 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, 9:1 to hexanes/EtOAc 8:2) gave the title compound (600 mg, 4% (2 steps), 7-fluoro isomer) as a light, yellow solid: 1H NMR (300 MHz, CDCl3) δ 7.59 (d, J=8.0 Hz, 1H), 7.41 (ddd, J=8.0, 8.0, 4.9 Hz, 1H), 7.10 (dd, J=9.1, 9.1 Hz, 1H), 5.00 (d, J=6.2 Hz, 2H), 2.04 (t, J=6.5 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, 9:1 to hexanes/EtOAc 8:2)

Sources & evidence

ORD record
ord-9639bfca526f44d385098acf98e10663
Source dataset
uspto-grants-2013_05
Patent number
US08450307B2

Reaction notes

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