Dimethylformamide → HCID 58779366, compound

HRID 1372144Notes

Reaction equation

HRID 1372144 reaction equation
Br[C:2]1[C:10]2[S:9][CH:8]=[CH:7][C:6]=2[C:5]([C:11]2[CH:16]=[CH:15][C:14]([O:17][CH3:18])=[CH:13][CH:12]=2)=[CH:4][CH:3]=1.[Li]CCCC.CN([CH:27]=[O:28])C.COC1C=CC(C2C3C=C(C=O)SC=3C=CC=2)=CC=1>C1COCC1>[CH3:18][O:17][C:14]1[CH:15]=[CH:16][C:11]([C:5]2[C:6]3[CH:7]=[CH:8][S:9][C:10]=3[C:2]([CH:27]=[O:28])=[CH:3][CH:4]=2)=[CH:12][CH:13]=1

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 21071799HCID 21071799, compoundHCID 86011565HCID 86011565, compoundHCID 178418339Butyllithium

Product 1

HCID 58779366HCID 58779366, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a 25 ml round bottom flask was added 7-bromo-4-(4-methoxyphenyl)-1-benzothiophene (300 mg, 0.94 mmol) to anhydrous THF (10 ml) and the solution was cooled to −78° C. n-BuLi (0.38 ml of 2.5 M in hexanes, 0.94 mmol) was added dropwise and the solution was stirred for 10 min after which anhydrous DMF (0.15 ml, 1.9 mmol) was added all at once at −78° C. The reaction was stirred for 15 min then quenched with water (10 ml) and extracted with ether. The organic layers were combined, dried over anhydrous Na2SO4, and concentrated to 180 mg (71.4%) of aldehyde products as a yellow oil. Reverse phase HPLC (CH3CN 0.1% TFA, water 0.1% TFA) produced 160 mg of a 8:3 mixture of desired product and 4-(4-methoxyphenyl)-1-benzothiophene-2-carbaldehyde as a single peak. Another side product (7-bromo-4-(4-methoxyphenyl)-1-benzothiophene-2-carbaldehyde, 20 mg) was collected: 1H NMR (8:3 ratio of desired+7-bromo-4-(4-methoxyphenyl)-1-benzothiophene-2-carbaldehyde) (300 MHz, DMSO-d6): δ 3.86 (3H, s, desired+minor), 7.14 (2H, d, J=8.9 Hz, minor), 7.14 (2H, d, J=8.6 Hz, desired), 7.47 (1H, d, J=7.3 Hz, minor), 7.54–7.67 (4H, m, desired+minor), 7.99 (1H, d, J=5.6 Hz, desired), 8.09 (1H, d, J=8.1 Hz, minor), 8.19 (1H, d, J=7.5 Hz), 8.41 (1H, s, minor), 10.14 (1H, s, minor), 10.27 (1H, s, desired). Anal. for C16H12O2S:

Workup

  1. additionwas added dropwise
  2. additionwas added all at once at −78° C
  3. customthen quenched with water (10 ml)
  4. extractionextracted with ether
  5. dry with materialdried over anhydrous Na2SO4
  6. concentrationconcentrated to 180 mg (71.4%) of aldehyde products as a yellow oil
  7. customReverse phase HPLC (CH3CN 0.1% TFA, water 0.1% TFA) produced

Sources & evidence

ORD record
ord-d6f6e1760a72418d96182db359add197
Source dataset
uspto-grants-2007_01
Patent number
US07157491B2

Reaction notes

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