Triethylamine → (1r/s,6r/s)-n-(Cyanomethyl)-6-{[(4-fluorophenyl)sulfanyl]methyl}-cyclohex-3-ene-1-carboxamide

HRID 2222920Notes

Reaction equation

HRID 2222920 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([S:8][CH2:9][CH:10]2[CH:15]([C:16]([OH:18])=O)[CH2:14][CH:13]=[CH:12][CH2:11]2)=[CH:4][CH:3]=1.Cl.[NH2:20][CH2:21][C:22]#[N:23].F[P-](F)(F)(F)(F)F.N1([PH+](N2CCCC2)N2CCCC2)CCCC1.C(N(CC)CC)C>CN(C)C=O>[C:21]([CH2:22][NH:23][C:16]([CH:15]1[CH:10]([CH2:9][S:8][C:5]2[CH:4]=[CH:3][C:2]([F:1])=[CH:7][CH:6]=2)[CH2:11][CH:12]=[CH:13][CH2:14]1)=[O:18])#[N:20]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 11491918Aminoacetonitrile hydrochlorideHCID 22226026Tripyrrolidinophosphonium hexafluorophosphateHCID 86596137(1r/s,6r/s)-6-{[(4-Fluorophenyl)sulfanyl]methyl}cyclohex-3-ene-1-carboxylic acid

Product 1

HCID 59711790(1r/s,6r/s)-n-(Cyanomethyl)-6-{[(4-fluorophenyl)sulfanyl]methyl}-cyclohex-3-ene-1-carboxamide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

(1R/S,6R/S)-6-{[(4-Fluorophenyl)sulfanyl]methyl}cyclohex-3-ene-1-carboxylic acid (620 mg, 2.34 mmol) was weighed into a 25 mL round bottom flask and aminoacetonitrile hydrochloride (480 mg, 5.20 mmol) and benzotriazol-1-yloxy)tripyrrolidinophosphonium hexafluorophosphate (1.34 g, 2.60 mmol) were added. Dimethylformamide (8.0 mL) was added and the reaction mixture was cooled to 0° C. After adding triethylamine (1.2 mL, 8.6 mmol) the reaction mixture was stirred at ambient temperature for 28 h, and then partitioned between water and ethyl acetate. The organic layer was washed with saturated sodium chloride aqueous solution, dried over anhydrous sodium sulfate, and concentrated. Chromatography of the residue on silica gel with 45:55 ethyl acetate:hexanes eluent provided the title compound as a colorless solid. 1H NMR (500 MHz, acetone-d6): δ=7.92 (1H, br s), 7.41 (2H, dd), 7.08 (2H, dd), 5.64 (2H, m), 4.24 (2H, m), 3.22 (1H, dd), 2.72 (1H, dd), 2.50-2.40 (2H, m), 2.26-2.20 (2H, m), 2.12 (1H, m), 1.86 (1H, m). MS [ESI, (M−H)−] m/z=303.1 amu.

Workup

  1. custompartitioned between water and ethyl acetate
  2. washThe organic layer was washed with saturated sodium chloride aqueous solution
  3. dry with materialdried over anhydrous sodium sulfate
  4. concentrationconcentrated

Sources & evidence

ORD record
ord-4b53f028ae854d9fb91a59ac848fc9b9
Source dataset
uspto-grants-2008_05
Patent number
US07371747B2

Reaction notes

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