Benzoyl isothiocyanate → N-(((3 S,4R,5 S)-3-(2,3-Difluorophenyl)-4-(hydroxymethyl)-5-(trifluoromethyl)tetrahydrofuran-3-yl)carbamothioyl)benzamide

HRID 2045850Notes

Reaction equation

HRID 2045850 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:24]2[CH:29]=[CH:28][CH:27]=[C:26]([F:30])[C:25]=2[F:31])[CH2:17][O:16][C@H:15]([C:18]([F:21])([F:20])[F:19])[C@H:14]1[CH2:22][OH:23].C(=O)(O)[O-].[Na+]>C(Cl)Cl>[F:31][C:25]1[C:26]([F:30])=[CH:27][CH:28]=[CH:29][C:24]=1[C@@:13]1([NH:12][C:10]([NH:9][C:1](=[O:8])[C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)=[S:11])[C@H:14]([CH2:22][OH:23])[C@@H:15]([C:18]([F:21])([F:19])[F:20])[O:16][CH2:17]1

Participants

5

Reactant 3

HCID 68284Benzoyl isothiocyanateHCID 516892Sodium BicarbonateHCID 70496186((2S,3R,4S)-4-amino-4-(2,3-difluorophenyl)-2-(trifluoromethyl)tetrahydrofuran-3-yl)methanol

Product 1

HCID 86668364N-(((3 S,4R,5 S)-3-(2,3-Difluorophenyl)-4-(hydroxymethyl)-5-(trifluoromethyl)tetrahydrofuran-3-yl)carbamothioyl)benzamide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Benzoyl isothiocyanate (2.0 mL) was added to a solution containing ((2S,3R,4S)-4-amino-4-(2,3-difluorophenyl)-2-(trifluoromethyl)tetrahydrofuran-3-yl)methanol (3.12 g) in DCM (20 mL), and the mixture was stirred at RT for 18 h. Sodium bicarbonate (sat., aq., 50 mL) was then added, the mixture extracted with EtOAc (3×75 mL), dried over MgSO4 and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (5% to 40% EtOAc in hexanes) to obtain the title compound (4.18 g). 1H NMR (400 MHz, CDCl3) δ ppm 3.12 (dd, J=7.6, 4.3 Hz, 1H), 3.18-3.29 (m, 1H), 4.03 (ddd, J=12.3, 7.2, 4.5 Hz, 1H), 4.35-4.49 (m, 1H), 4.59 (d, J=9.9 Hz, 1H), 4.81 (d, J=9.6 Hz, 1H), 7.07-7.23 (m, 2H), 7.49 (t, J=7.2 Hz, 1H), 7.56 (t, J=7.7 Hz, 2H), 7.67 (t, J=7.5 Hz, 1H), 7.88 (d, J=7.1 Hz, 2H), 8.92 (s, 1H), 11.89 (s, 1H)

Workup

  1. extractionthe mixture extracted with EtOAc (3×75 mL)
  2. dry with materialdried over MgSO4
  3. concentrationconcentrated under reduced pressure
  4. customThe residue was purified by silica gel column chromatography (5% to 40% EtOAc in hexanes)

Sources & evidence

ORD record
ord-314d23b5314149f89e626c1a2afa40d1
Source dataset
uspto-grants-2013_11
Patent number
US08592408B2

Reaction notes

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