Dichloromethane → tert-Butyl 3-(benzoylcarbamothioylamino)-4-(hydroxymethyl)-3-phenyl-pyrrolidine-1-carboxylate

HRID 338113Notes

Reaction equation

HRID 338113 reaction equation
[C:1]([N:9]=[C:10]=[S:11])(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[NH2:12][C:13]1([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[CH:17]([CH2:18][OH:19])[CH2:16][N:15]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:14]1.C(=O)(O)[O-].[Na+].ClCCl>O1CCCC1>[C:1]([NH:9][C:10]([NH:12][C:13]1([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[CH:17]([CH2:18][OH:19])[CH2:16][N:15]([C:20]([O:22][C:23]([CH3:26])([CH3:24])[CH3:25])=[O:21])[CH2:14]1)=[S:11])(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 6344DichloromethaneHCID 68284Benzoyl isothiocyanate2×HCID 516892Sodium BicarbonateHCID 86697911tert-Butyl 3-amino-4-(hydroxymethyl)-3-phenyl-pyrrolidine-1-carboxylate

Product 1

HCID 86697928tert-Butyl 3-(benzoylcarbamothioylamino)-4-(hydroxymethyl)-3-phenyl-pyrrolidine-1-carboxylateYield 68%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Benzoyl isothiocyanate (81.37 μL, 603.33 mmol) is added to a 0° C. solution of tert-butyl 3-amino-4-(hydroxymethyl)-3-phenyl-pyrrolidine-1-carboxylate (0.168 g, 574.60 mmol) in tetrahydrofuran (2.3 mL). The mixture is warmed to room temperature and stirred overnight. Benzoyl isothiocyanate (15.50 μL, 114.92 mmol) is added and the mixture is stirred for 2 hr. Sodium bicarbonate solution and dichloromethane are added and the aqueous layer is separated, the aqueous mixture is extracted with dichloromethane (3×25 mL), dried over sodium sulfate, filtered, and concentrated to dryness. The crude product is purified via silica gel chromatography eluting with 0-100% ethyl acetate/hexanes to give the title compound (0.178 g, 68%). ES/MS (m/e): 454.3 (M−1).

Workup

  1. stirringthe mixture is stirred for 2 hr
  2. customthe aqueous layer is separated
  3. extractionthe aqueous mixture is extracted with dichloromethane (3×25 mL)
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated to dryness
  7. customThe crude product is purified via silica gel chromatography
  8. washeluting with 0-100% ethyl acetate/hexanes

Sources & evidence

ORD record
ord-d4e8dcc5c69b40119ca3d61f00123e00
Source dataset
uspto-grants-2014_11
Patent number
US08889856B2

Reaction notes

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