Cesium carbonate → trans-N-cyanomethyl-2-(4-fluorophenylsulfanylmethyl)-cyclohexanecarboxamide

HRID 2222895Notes

Reaction equation

HRID 2222895 reaction equation
Br[CH2:2][C@@H:3]1[CH2:8][CH2:7][CH2:6][CH2:5][C@H:4]1[C:9]([NH:11][CH2:12][C:13]#[N:14])=[O:10].C(=O)([O-])[O-].[Cs+].[Cs+].[F:21][C:22]1[CH:27]=[CH:26][C:25]([SH:28])=[CH:24][CH:23]=1>CC(C)=O>[C:13]([CH2:12][NH:11][C:9]([C@@H:4]1[CH2:5][CH2:6][CH2:7][CH2:8][C@H:3]1[CH2:2][S:28][C:25]1[CH:26]=[CH:27][C:22]([F:21])=[CH:23][CH:24]=1)=[O:10])#[N:14]

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 677894-FluorothiophenolHCID 86596125trans-2-Bromomethyl-N-cyanomethylcyclohexanecarboxamide

Product 1

HCID 9901142trans-N-cyanomethyl-2-(4-fluorophenylsulfanylmethyl)-cyclohexanecarboxamide

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent2×

Conditions

Temperature
50 °C

Procedure

trans-2-Bromomethyl-N-cyanomethylcyclohexanecarboxamide (262 mg, 1 mmol) and cesium carbonate (331 mg, 1.02 mmol) were weighed into a 15 mL test tube fitted with a stir bar and vented cap and then acetone (3 mL) and 4-fluorobenzenethiol (106 μL, 1.01 mmol) were added sequentially to the test tube. The reaction mixture was stirred at 50° C. overnight and then diluted with hot acetone (7 mL). The reaction mixture was filtered through Celite™ and the filter funnel and Celite™ were washed with hot acetone (25 mL). The combined filtrate and wash were concentrated on a rotary evaporator and product was purified from the residue by chromatography on 40 cm3 of silica gel in a 2×13 cm column with 9:1 dichloromethane:ethyl acetate eluent. The product fractions were concentrated on a rotary evaporator and the residue dried under high vacuum to give trans-N-cyanomethyl-2-(4-fluorophenylsulfanylmethyl)-cyclohexanecarboxamide as a waxy white solid. 1H NMR (DMSO-d6): δ 8.64 (1H, t), 7.33 (2H, m), 7.14 (2H, m), 4.13 (2H, d), 2.96 (1H, dd), 2.57 (1H, dd), 2.05 (2H, m), 1.70 (4H, m), 1.15 (4H, m). MS [ESI, (M−H)−] m/z=305.0 amu.

Workup

  1. customfitted with a stir bar
  2. customvented cap
  3. filtrationThe reaction mixture was filtered through Celite™
  4. washthe filter funnel and Celite™ were washed with hot acetone (25 mL)
  5. washThe combined filtrate and wash
  6. concentrationwere concentrated on a rotary evaporator and product
  7. customwas purified from the residue by chromatography on 40 cm3 of silica gel in a 2×13 cm column with 9:1 dichloromethane
  8. concentrationThe product fractions were concentrated on a rotary evaporator
  9. customthe residue dried under high vacuum

Sources & evidence

ORD record
ord-aaf85cea8e39462182c9df7f8c955bb0
Source dataset
uspto-grants-2008_05
Patent number
US07371747B2

Reaction notes

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