Sodium Iodide → HCID 58516939, compound

HRID 1428165Notes

Reaction equation

HRID 1428165 reaction equation
[S:1]1[CH:9]2[C:4]([CH2:5][NH:6][CH2:7][CH2:8]2)=[CH:3][C:2]1=[O:10].[Si:11](Cl)([C:14]([CH3:17])([CH3:16])[CH3:15])([CH3:13])[CH3:12].[I-].[Na+].Br[CH:22]([C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][C:29]=1[F:34])[C:23]([CH:25]1[CH2:27][CH2:26]1)=[O:24]>ClCCl.CO.C(OCC)(=O)C.C(N(CC)CC)C>[Si:11]([O:10][C:2]1[S:1][C:9]2[CH2:8][CH2:7][N:6]([CH:22]([C:23]([CH:25]3[CH2:27][CH2:26]3)=[O:24])[C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][C:29]=3[F:34])[CH2:5][C:4]=2[CH:3]=1)([C:14]([CH3:17])([CH3:16])[CH3:15])([CH3:13])[CH3:12]

Participants

8

Reactant 4

HCID 5238Sodium IodideHCID 28928tert-Butyldimethylsilyl chlorideHCID 137484635,6,7,7a-Tetrahydrothieno[3,2-c]pyridin-2(4H)-oneHCID 234358712-Bromo-1-cyclopropyl-2-(2-fluorophenyl)ethan-1-one

Product 1

HCID 58516939HCID 58516939, compound

Reagents, catalysts & solvents 3

HCID 6344DichloromethaneSolvent2×HCID 8471TriethylamineSolvent2×HCID 21584119Ethylacetate methanolSolvent2×

Conditions

Temperature
10 °C

Procedure

5,6,7,7a-Tetrahydro-4H-thieno[3,2-c]pyridin-2-one (2.0 g) was added to dichloromethane (10 mL) and stirred for 10 minutes at 10° C. Triethylamine (1.22 g) was then added and the mixture was stirred for 15 minutes to form a reaction mixture. Tert-butyldimethylsilyl chloride (1.81 g) dissolved in dichloromethane was added to the mixture at 10° C. The mixture was stirred at 10° C. and the reaction was monitored by Thin Layer Chromatography (TLC) (methanol/ethyl acetate=3/7) until the reaction was completed. Triethylamine (2.12 g), sodium iodide (0.02 g) and 2-bromo-2-(2-fluorophenyl)-1-cyclopropyl-ethanone (1.5 molar eq.) were added slowly to the reaction mixture at 10° C. The reaction mixture was stirred at 25° C. and the reaction was monitored by Thin Layer Chromatography (TLC) (methanol/ethyl acetate=3/7). After the reaction was completed, the organic phase was then washed with phosphate buffer (pH 6-7), and concentrated under reduced pressure at 30° C. to obtain 2-(tert-butyldimethylsilyloxy)-5-(α-cyclopropylformyl-2-fluorobenzyl)-4,5,6,7-tetrahydrothieno[3,2-c]pyridine as a crude product. The crude product (1 g) was recrystallized using acetone/water (1:1 v/v) (acetone volume=10 ml) at −5° C. for 3 hours for the crystallization method. Crystal precipitate was collected by filtration and dried under vacuum at 50° C. for 24 hours to obtain (tert-butyldimethylsilyloxy)-5-(α-cyclopropylformyl-2-fluorobenzyl)-4,5,6,7-tetrahydro-thieno[3,2-c]pyridine with the HPLC purity of 96%. The yield was 90%.

Workup

  1. stirringthe mixture was stirred for 15 minutes
  2. customto form a reaction mixture
  3. additionwas added to the mixture at 10° C
  4. stirringThe mixture was stirred at 10° C.
  5. stirringThe reaction mixture was stirred at 25° C.
  6. washthe organic phase was then washed with phosphate buffer (pH 6-7)
  7. concentrationconcentrated under reduced pressure at 30° C.

Sources & evidence

ORD record
ord-f5d854788f9247aa8ea0c1aa277733e4
Source dataset
uspto-grants-2015_01
Patent number
US08937053B2

Reaction notes

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