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

HRID 1429619Notes

Reaction equation

HRID 1429619 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, 1 H), 3.18-3.29 (m, 1 H), 4.03 (ddd, J=12.3, 7.2, 4.5 Hz, 1 H), 4.35-4.49 (m, 1 H), 4.59 (d, J=9.9 Hz, 1 H), 4.81 (d, J=9.6 Hz, 1 H), 7.07-7.23 (m, 2 H), 7.49 (t, J=7.2 Hz, 1 H), 7.56 (t, J=7.7 Hz, 2 H), 7.67 (t, J=7.5 Hz, 1 H), 7.88 (d, J=7.1 Hz, 2 H), 8.92 (s, 1 H), 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-d40059847b3d47f991174d764ce8288b
Source dataset
uspto-grants-2015_01
Patent number
US08940734B2

Reaction notes

Loading…