Dichloromethane → HCID 86684920, compound

HRID 2402920Notes

Reaction equation

HRID 2402920 reaction equation
[C:1]([C:3]1([NH:6][C:7]([C@H:9]2[N:13]([C:14]([C:16]3([C:19]([F:22])([F:21])[F:20])[CH2:18][CH2:17]3)=[O:15])[CH2:12][C@@H:11](OS(C)(=O)=O)[CH2:10]2)=[O:8])[CH2:5][CH2:4]1)#[N:2].Cl.[CH3:29][C:30]1[CH:35]=[C:34]([C:36]2[CH:41]=[CH:40][C:39]([SH:42])=[C:38]([C:43]([F:46])([F:45])[F:44])[CH:37]=2)[CH:33]=[CH:32][N:31]=1.CC(C)([O-])C.[Na+].ClCCl>C1COCC1>[C:1]([C:3]1([NH:6][C:7]([C@@H:9]2[CH2:10][C@@H:11]([S:42][C:39]3[CH:40]=[CH:41][C:36]([C:34]4[CH:33]=[CH:32][N:31]=[C:30]([CH3:29])[CH:35]=4)=[CH:37][C:38]=3[C:43]([F:46])([F:44])[F:45])[CH2:12][N:13]2[C:14]([C:16]2([C:19]([F:21])([F:22])[F:20])[CH2:17][CH2:18]2)=[O:15])=[O:8])[CH2:4][CH2:5]1)#[N:2]

Participants

6

Reactant 4

HCID 6344DichloromethaneHCID 23676156Sodium t-butoxideHCID 86684924HCID 86684924, compoundHCID 136387778HCID 136387778, compound

Product 1

HCID 86684920HCID 86684920, compoundYield 106.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
50 °C

Procedure

To a stirred suspension of methanesulfonic acid (3S,5S)-5-(1-cyano-cyclopropylcarbamoyl)-1-(1-trifluoromethyl-cyclopropanecarbonyl)-pyrrolidin-3-yl ester (20.5 g, 50 mmol) and 4-(2-methyl-pyridin-4-yl)-2-trifluoromethyl-benzenethiol hydrochloride (17.6 g, 57.5 mmol) in THF (75 mL) was added at 0° C. 25% sodium tert-butoxide in THF (43.2 g, 112.5 mmol) over 30 min and the reaction mixture was stirred at 50° C. for 4.5 h. After cooling to 10° C., the reaction mixture was added to dichloromethane (250 mL) and washed twice with deionized water (2×250 mL). The organic layer was dried (Na2SO4), filtered, and evaporated by rotary evaporation (45° C./≧10 mbar), affording the crude title product (30.9 g, 106%) as a beige, amorphous foam which was used without further purification in the next step. 1H NMR (CDCl3, 400 MHz) δ 1.10-1.35 (m, 6H), 1.47-1.58 (m, 2H), 2.00-2.11 (m, 1H), 2.65 (s, 3H), 2.92-3.01 (m, 1H), 3.92 & 4.02 (ABC, JAB=11.8 Hz, JAC=5.0 Hz, JBC=6.2 Hz, each 1H), 4.17 (quint, J=5.5 Hz, 1H), 4.72 (dd, J1=8.1 Hz, J2=4.8 Hz, 1H), 7.31 (dd, J1=5.1 Hz, J2=1.5 Hz, 1H), 7.37 (s, 1H), 7.62 (s, 1H), 7.66 (d, J=8.3 Hz, 1H), 7.80 (dd, J1=8.1 Hz, J2=1.9 Hz, 1H), 7.93 (d, J=2.1 Hz, 1H), 8.60 (d, J=5.1 Hz, 1H). ESI-MS (m/z) [M+H]+ 583 (40).

Workup

  1. additionwas added at 0° C
  2. temperatureAfter cooling to 10° C.
  3. washwashed twice with deionized water (2×250 mL)
  4. dry with materialThe organic layer was dried (Na2SO4)
  5. filtrationfiltered
  6. customevaporated by rotary evaporation (45° C./≧10 mbar)

Sources & evidence

ORD record
ord-2c6aeb28976d40dbb7aa54ca524b44de
Source dataset
uspto-grants-2014_08
Patent number
US08796471B2

Reaction notes

Loading…