Sodium Iodide → HCID 58516939, compound

HRID 1428163Notes

Reaction equation

HRID 1428163 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×

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 to form a solution at 25° C. followed by dropwise addition of triethylamine (1.22 g) to the solution. After the reaction mixture was stirred for 15 minutes, a solution of tert-butyldimethylsilyl chloride (1.81 g) in dichloromethane was added to the reaction mixture at the same temperature. The reaction mixture was stirred at 25° C. until the reaction was completed which was monitored by Thin Layer Chromatography (TLC) (methanol/ethyl acetate=3/7). Triethylamine (2.12 g), sodium iodide (0.02 g) and 2-bromo-2-(2-fluorophenyl)-1-cyclopropylethanone (2.96 g) were then added to the mixture 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 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 dissolved in acetone/water (2:1 v/v, acetone volume=8 ml) and the mixture was kept at −5° C. for 3 hours for the crystallization method. The crystals were collected by filtration and dried in vacuum at 50° C. for 24 hours to obtain (tert-butyldimethylsilyloxy)-5-(α-cyclopropylformyl-2-fluorobenzyl)-4,5,6,7-tetrahydrothieno[3,2-c]pyridine having the HPLC purity of 99%. The yield was 85%.

Workup

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

Sources & evidence

ORD record
ord-9094deb7b43b426b8e646a007f8d1eae
Source dataset
uspto-grants-2015_01
Patent number
US08937053B2

Reaction notes

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