Sodium Bicarbonate → HCID 86762224, compound

HRID 1619022Notes

Reaction equation

HRID 1619022 reaction equation
[C:1]([NH:9][C:10]([NH:12][C:13]1([C:27]2[S:28][CH:29]=[CH:30][CH:31]=2)[CH:17]([CH2:18]O)[CH2:16][N:15]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:14]1)=[S:11])(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.ClC(N(C)C)=C(C)C.C(=O)(O)[O-].[Na+]>ClCCl>[C:1]([NH:9][C:10]1[S:11][CH2:18][C@@H:17]2[CH2:16][N:15]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:14][C@:13]2([C:27]2[S:28][CH:29]=[CH:30][CH:31]=2)[N:12]=1)(=[O:8])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 516892Sodium BicarbonateHCID 6407921-Chloro-N,N-2-trimethylpropenylamineHCID 86697929HCID 86697929, compound

Product 1

HCID 86762224HCID 86762224, compoundYield 90.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of racemic tert-butyl 3-(benzoylcarbamothioylamino)-4-(hydroxymethyl)-3-(2-thienyl)pyrrolidine-1-carboxylate (3.8 g, 8.23 mmol) in dichloromethane (206 mL) cooled to 0° C. is added drop wise 1-chloro-N,N,2-trimethylpropenylamine (2.18 mL, 16.46 mmol). The reaction is warmed to room temperature and is stirred for 2 hours. To the reaction mixture is added a saturated solution of sodium bicarbonate and dichloromethane. The mixture is extracted with dichloromethane. The organic layers are combined, dried over sodium sulfate, filtered, and concentrated to give a residue. The residue is purified by silica gel flash chromatography, eluting with hexane/ethyl acetate (1:0) to hexane/ethyl acetate (0:1) to give the title compound (3.30 g, 90%). ES/MS (m/e): 444 (M+H). The racemic tert-butyl-3-(benzoylcarbamothioylamino)-4-(hydroxymethyl)-3-phenyl-pyrrolidine-1-carboxylate (3.2 g, 7.4 mmol) is dissolved in methanol/chloroform (36 ml/25 ml) and is separated into its constituent enantiomers by chiral SFC (Chiralpak OJ-H 50×250 mm; eluent: 25% methanol in 75% CO2; flow 300 g/min at UV 240 nm; column temperature −40° C.; 0.64 g/injection). Analysis of isolated enantiomer (Chiralpak OJ-H 4.6×150 mm; eluent: 25% methanol in 75% CO2; flow 5 mL/min at UV 240 nm, column temperature −35° C.) gave the title compound with Rt=1.5 min, isomer 1, (1.27 g, 39%, >99% ee).

Workup

  1. extractionThe mixture is extracted with dichloromethane
  2. dry with materialdried over sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customto give a residue
  6. customThe residue is purified by silica gel flash chromatography
  7. washeluting with hexane/ethyl acetate (1:0) to hexane/ethyl acetate (0:1)

Sources & evidence

ORD record
ord-695928087bca45bda91bb8242d3ea71c
Source dataset
uspto-grants-2014_07
Patent number
US08772282B2

Reaction notes

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