Sodium t-butoxide → HCID 86684922, compound

HRID 2402917Notes

Reaction equation

HRID 2402917 reaction equation
[CH3:1][N:2]1[CH:6]=[C:5]([C:7]2[CH:12]=[CH:11][C:10]([S:13]CCC(N)=O)=[C:9]([C:19]([F:22])([F:21])[F:20])[CH:8]=2)[CH:4]=[N:3]1.CC(C)([O-])C.[Na+].[C:29]([C:31]1([NH:34][C:35]([C@H:37]2[N:41]([C:42]([C:44]3([C:47]([F:50])([F:49])[F:48])[CH2:46][CH2:45]3)=[O:43])[CH2:40][C@@H:39](OS(C3C=CC=CC=3)(=O)=O)[CH2:38]2)=[O:36])[CH2:33][CH2:32]1)#[N:30]>O1CCCC1.CN(C)C(=O)C.O>[C:29]([C:31]1([NH:34][C:35]([C@@H:37]2[CH2:38][C@@H:39]([S:13][C:10]3[CH:11]=[CH:12][C:7]([C:5]4[CH:4]=[N:3][N:2]([CH3:1])[CH:6]=4)=[CH:8][C:9]=3[C:19]([F:21])([F:20])[F:22])[CH2:40][N:41]2[C:42]([C:44]2([C:47]([F:49])([F:50])[F:48])[CH2:46][CH2:45]2)=[O:43])=[O:36])[CH2:33][CH2:32]1)#[N:30]

Participants

7

Reactant 3

HCID 23676156Sodium t-butoxideHCID 86684911HCID 86684911, compoundHCID 86684916HCID 86684916, compound

Product 1

HCID 86684922HCID 86684922, compoundYield 111.8%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 31374DimethylacetamideSolvent2×

Procedure

3-[4-(1-Methyl-1H-pyrazol-4-yl)-2-trifluoromethyl-phenylsulfanyl]-propionamide (16.3 g, 49.6 mmol) was dissolved in tetrahydrofuran (80 mL) before sodium tert-butoxide (4.7 g, 48.9 mmol) was added and the fine suspension was stirred for 2 h at room temperature. N,N-dimethylacetamide (40 mL) was added and the mixture was stirred for further 2.5 h at room temperature. A solution of benzenesulfonic acid (3S,5S)-5-(1-cyano-cyclopropylcarbamoyl)-1-(1-trifluoromethyl-cyclopropanecarbonyl)-pyrrolidin-3-yl ester (20 g, 42.4 mmol) in N,N-dimethylacetamide (40 mL) was added and the yellow, fine suspension was stirred for 42 h at room temperature. The mixture was diluted with water (240 mL) and extracted with tert-butyl methyl ether (1×160 mL, 3×80 mL). The combined organic extracts were washed with an aqueous sodium carbonate solution (1 M, 80 mL) and brine (80 mL), dried over sodium sulfate and concentrated in vacuo to yield the title compound as a light brown foam (27.1 g). The crude product (containing dimethylacetamide) was used in the next step without further purification. For characterization purposes, a 2 g sample of crude material was purified by column chromagraphy on silica gel (eluent: gradient ethyl acetate/heptane 4:1 (v/v) to ethyl acetate). Likewise, 1.7 g of purified material were obtained. MS (ESI & APCI): m/z=572.1 [M+H]+, 589.2 [M+NH4]+. 1H NMR (CDCl3, 600 MHz): δ 1.12-1.22 (m, 3H), 1.28-1.34 (m, 3H), 1.49-1.54 (m, 2H), 2.02 (ddd, J=5.6 Hz, 8.2 Hz, 13.6 Hz, 1H), 2.88 (ddd, J=5.7 Hz, 5.7 Hz, 13.7 Hz, 1H), 3.89-3.99 (m, 2H), 3.97 (s, 3H), 4.04-4.09 (m, 1H), 4.69 (dd, J=5.2 Hz, 8.2 Hz, 1H), 7.55 (d, J=8.2 Hz, 1H), 7.60 (bs, 1H), 7.62 (dd, J=1.8 Hz, 8.2 Hz, 1H), 7.69 (s, 1H), 7.77 (d, J=1.8 Hz, 1H), 7.79 (s, 1H).

Workup

  1. additionwas added
  2. stirringthe mixture was stirred for further 2.5 h at room temperature
  3. stirringthe yellow, fine suspension was stirred for 42 h at room temperature
  4. extractionextracted with tert-butyl methyl ether (1×160 mL, 3×80 mL)
  5. washThe combined organic extracts were washed with an aqueous sodium carbonate solution (1 M, 80 mL) and brine (80 mL)
  6. dry with materialdried over sodium sulfate
  7. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-8d8bd205eb784911bed87fbe6fcd5740
Source dataset
uspto-grants-2014_08
Patent number
US08796471B2

Reaction notes

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