Sodium t-butoxide → HCID 86684920, compound

HRID 2402916Notes

Reaction equation

HRID 2402916 reaction equation
[CH3:1][C:2]1[CH:7]=[C:6]([C:8]2[CH:13]=[CH:12][C:11]([S:14]CCC(N)=O)=[C:10]([C:20]([F:23])([F:22])[F:21])[CH:9]=2)[CH:5]=[CH:4][N:3]=1.CC(C)([O-])C.[Na+].[C:30]([C:32]1([NH:35][C:36]([C@H:38]2[N:42]([C:43]([C:45]3([C:48]([F:51])([F:50])[F:49])[CH2:47][CH2:46]3)=[O:44])[CH2:41][C@@H:40](OS(C3C=CC=CC=3)(=O)=O)[CH2:39]2)=[O:37])[CH2:34][CH2:33]1)#[N:31]>O1CCCC1.CN(C)C(=O)C.O>[C:30]([C:32]1([NH:35][C:36]([C@@H:38]2[CH2:39][C@@H:40]([S:14][C:11]3[CH:12]=[CH:13][C:8]([C:6]4[CH:5]=[CH:4][N:3]=[C:2]([CH3:1])[CH:7]=4)=[CH:9][C:10]=3[C:20]([F:22])([F:21])[F:23])[CH2:41][N:42]2[C:43]([C:45]2([C:48]([F:51])([F:49])[F:50])[CH2:46][CH2:47]2)=[O:44])=[O:37])[CH2:33][CH2:34]1)#[N:31]

Participants

7

Reactant 3

HCID 23676156Sodium t-butoxideHCID 86684916HCID 86684916, compoundHCID 86684921HCID 86684921, compound

Product 1

HCID 86684920HCID 86684920, compoundYield 111.6%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 31374DimethylacetamideSolvent2×

Procedure

3-[4-(2-Methyl-pyridin-4-yl)-2-trifluoromethyl-phenylsulfanyl]-propionamide (200 g, 588 mmol) was dissolved in tetrahydrofuran (1.0 L) before sodium tert-butoxide (55.5 g, 578 mmol) was added and the fine suspension was stirred for 2 h at room temperature. N,N-dimethylacetamide (500 mL) was added and the solution was stirred for further 1.5 h. A solution of benzenesulfonic acid (3S,5S)-5-(1-cyano-cyclopropylcarbamoyl)-1-(1-trifluoromethyl-cyclopropanecarbonyl)-pyrrolidin-3-yl ester (237.5 g, 504 mmol) in N,N-dimethylacetamide (500 mL) was added and the brown, clear solution was stirred for 40 h. The mixture was diluted with water (3 L) and extracted with tert-butyl methyl ether (1×2 L, 3×1 L). The combined organic extracts were washed with an aqueous sodium carbonate solution (1 M, 1.0 L) and brine (1.0 L), dried over sodium sulfate, and concentrated in vacuo to yield the title compound as a brown gum (327.8 g). The crude product (containing dimethylacetamide) was used in the next step without further purification. For characterization purposes, a 4 g sample of crude material was purified by filtration over silica gel (20 g, eluent: ethyl acetate (200 mL)). 3.3 g of purified material were obtained as an off-white solid. MS (EI): m/z=583.1 [M+H]+. 1H NMR (CDCl3, 300 MHz): δ 1.10-1.36 (m, 6H), 1.49-1.58 (m, 2H), 1.99-2.12 (m, 1H), 2.65 (s, 3H), 2.90-3.02 (m, 1H), 3.92 & 4.02 (ABX, JAB=11.9 Hz, JAX=4.8 Hz, JBX=5.8 Hz, each 1H), 4.12-4.22 (m, 1H), 4.71 (dd, J=4.7 Hz, 7.8 Hz, 1H), 7.31 (d, J=5.3 Hz, 1H), 7.37 (br s, 1H), 7.60-7.69 (m, 2H), 7.80 (d, J=8.3 Hz, 1H), 7.93 (s, 1H), 8.60 (d, J=5.1 Hz, 1H).

Workup

  1. additionwas added
  2. stirringthe solution was stirred for further 1.5 h
  3. stirringthe brown, clear solution was stirred for 40 h
  4. extractionextracted with tert-butyl methyl ether (1×2 L, 3×1 L)
  5. washThe combined organic extracts were washed with an aqueous sodium carbonate solution (1 M, 1.0 L) and brine (1.0 L)
  6. dry with materialdried over sodium sulfate
  7. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-6426678cefe6422e87ed69eac3834783
Source dataset
uspto-grants-2014_08
Patent number
US08796471B2

Reaction notes

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