Sodium t-butoxide → HCID 86684923, compound

HRID 2402919Notes

Reaction equation

HRID 2402919 reaction equation
[CH3:1][C:2]1[CH:7]=[C:6]([C:8]2[CH:13]=[CH:12][C:11]([S:14][CH2:15]CC(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([CH3:48])[CH2:47][CH2:46]3)=[O:44])[CH2:41][C@@H](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:15]([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([CH3:48])[CH2:46][CH2:47]2)=[O:44])=[O:37])[CH2:33][CH2:34]1)#[N:31]

Participants

7

Reactant 3

HCID 23676156Sodium t-butoxideHCID 86684918HCID 86684918, compoundHCID 86684921HCID 86684921, compound

Product 1

HCID 86684923HCID 86684923, compoundYield 110.6%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 31374DimethylacetamideSolvent2×

Procedure

3-[4-(2-Methyl-pyridin-4-yl)-2-trifluoromethyl-phenylsulfanyl]-propionamide (15.0 g, 44.1 mmol) was dissolved in tetrahydrofuran (75 mL), before sodium tert-butoxide (4.15 g, 43.2 mmol) was added and the fine suspension was stirred for 2 h at room temperature. N,N-dimethylacetamide (37 mL) was added and the solution was stirred for further 2 h. A solution of benzenesulfonic acid (3S,5S)-5-(1-cyano-cyclopropylcarbamoyl)-1-(1-methyl-cyclo-propanecarbonyl)-pyrrolidin-3-yl ester (15.7 g, 37.7 mmol) in N,N-dimethylacetamide (37 mL) was added and the brown, clear solution was stirred for 65 h at room temperature. After that, the mixture was diluted with cold water (240 mL) and extracted with tert-butyl methyl ether (1×180 mL, 5×90 mL). The combined organic extracts were washed with aqueous sodium carbonate solution (1 M, 90 mL) and brine (90 mL), dried over sodium sulfate and concentrated in vacuo to yield the title compound as a brown gum (22.05 g). The crude product (containing dimethylacetamide) was used in the next step without further purification. MS (EI): m/z=529.1 [M+H]+. 1H NMR (CDCl3, 400 MHz): δ 0.56-0.66 (m, 2H), 0.87-0.93 (m, 1H), 1.04-1.09 (m, 1H), 1.18-1.22 (m, 2H), 1.31 (s, 3H), 1.45-1.57 (m, 2H), 1.95-2.04 (m, 1H), 2.65 (s, 3H), 2.95-3.01 (m, 1H), 3.91 & 4.02 (ABX, JAB=11.3 Hz, JAX=5.6 Hz, JBX=6.5 Hz, each 1H), 4.14-4.22 (m, 1H), 4.66 (dd, J=4.3 Hz, 8.1 Hz, 1H), 7.31 (dd, J=1.5 Hz, 5.3 Hz, 1H), 7.37 (bs, 1H), 7.69 & 7.80 (ABX, JAB=8.2 Hz, JAX=0 Hz, JBX=2.0 Hz, each 1H), 7.93 (d, J=1.9 Hz, 1H), 8.06 (bs, 1H), 8.60 (d, J=5.1 Hz, 1H).

Workup

  1. additionwas added
  2. stirringthe solution was stirred for further 2 h
  3. stirringthe brown, clear solution was stirred for 65 h at room temperature
  4. extractionextracted with tert-butyl methyl ether (1×180 mL, 5×90 mL)
  5. washThe combined organic extracts were washed with aqueous sodium carbonate solution (1 M, 90 mL) and brine (90 mL)
  6. dry with materialdried over sodium sulfate
  7. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-726744dd1cfd49b4b63e8987d8e287ac
Source dataset
uspto-grants-2014_08
Patent number
US08796471B2

Reaction notes

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