1,2-Dichloroethane → N-cyanomethyl-4-morpholin-4-yl-4-oxo-2-(2-trifluoromethyl-benzyl-sulfonylmethyl)-butyramide

HRID 1830164Notes

Reaction equation

HRID 1830164 reaction equation
[N:1]1([C:7](=[O:28])[CH2:8][CH:9]([CH2:13][S:14]([CH2:17][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=2[C:24]([F:27])([F:26])[F:25])(=[O:16])=[O:15])[C:10]([OH:12])=O)[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.C(Cl)CCl.C1C=C[C:36]2[N:41](O)N=[N:39][C:37]=2C=1.Cl.NCC#N.CN1CCOCC1>>[C:37]([CH2:36][NH:41][C:10](=[O:12])[CH:9]([CH2:13][S:14]([CH2:17][C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=1[C:24]([F:27])([F:25])[F:26])(=[O:15])=[O:16])[CH2:8][C:7]([N:1]1[CH2:2][CH2:3][O:4][CH2:5][CH2:6]1)=[O:28])#[N:39]

Participants

6

Reactant 5

HCID 111,2-DichloroethaneHCID 79724-MethylmorpholineHCID 757711-HydroxybenzotriazoleHCID 11491918Aminoacetonitrile hydrochlorideHCID 220539894-Morpholin-4-yl-4-oxo-2-(2-trifluoromethyl-benzylsulfonylmethyl)-butyric acid

Product 1

HCID 21031064N-cyanomethyl-4-morpholin-4-yl-4-oxo-2-(2-trifluoromethyl-benzyl-sulfonylmethyl)-butyramideYield 71.9%

Procedure

A mixture comprised of 4-morpholin-4-yl-4-oxo-2-(2-trifluoromethyl-benzylsulfonylmethyl)-butyric acid (200 mg, 0.47 mmol), prepared as in reference 5, EDC (200 mg, 1.05 mmol), HOBt (200 mg, 1.3 mmol), and aminoacetonitrile hydrochloride (150 mg, 1.6 mmol) was treated with dichloromethyl (4 mL) and 4-methylmorpholine (0.5 mL). The mixture was stirred at ambient temperature for 2 hours. After dilution with ethyl acetate (150 mL), the solution was washed with water (30 mL), saturated aqueous NaHCO3 solution and brine, dried with magnesium sulfate and evaporated under vacuum. The product was crystallized from ethyl acetate/hexane to yield N-cyanomethyl-4-morpholin-4-yl-4-oxo-2-(2-trifluoromethyl-benzyl-sulfonylmethyl)-butyramide (156 mg) as a yellowish solid; 1H NMR: (DMSO) 8.87 (t, J=5.5 Hz, 1H), 7.81–7.57 (m, 4H), 4.74 (d, J=14.5 Hz, 1H), 4.67 (d, J=14.5 Hz, 1H), 4.13 (d, J=5.5 Hz, 2H), 3.63–3.26 (m, 11H), 2.75 (dd, J=6.4 Hz, J=16.8 Hz, 1H), 2.65 (dd, J=6.2 Hz, J=16.8 Hz, 1H); MS: (M++1) 462;

Workup

  1. washAfter dilution with ethyl acetate (150 mL), the solution was washed with water (30 mL), saturated aqueous NaHCO3 solution and brine
  2. dry with materialdried with magnesium sulfate
  3. customevaporated under vacuum
  4. customThe product was crystallized from ethyl acetate/hexane

Sources & evidence

ORD record
ord-fb522a0b528543ceabe0ff99bc3d69b8
Source dataset
uspto-grants-2006_06
Patent number
US07064123B1

Reaction notes

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