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

HRID 1429611Notes

Reaction equation

HRID 1429611 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]=[CH:26][C:25]=2[F:30])[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:30][C:25]1[CH:26]=[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:19])([F:20])[F:21])[O:16][CH2:17]1

Participants

5

Reactant 3

HCID 68284Benzoyl isothiocyanateHCID 516892Sodium BicarbonateHCID 66869282((2S,3R,4S)-4-amino-4-(2-fluorophenyl)-2-(trifluoromethyl)tetrahydrofuran-3-yl)methanol

Product 1

HCID 60169627N-(((3S,4R,5S)-3-(2-fluorophenyl)-4-(hydroxymethyl)-5-(trifluoromethyl)tetrahydrofuran-3-yl)carbamothioyl)benzamide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Benzoyl isothiocyanate (19.0 mL) was added to a solution containing ((2S,3R,45)-4-amino-4-(2-fluorophenyl)-2-(trifluoromethyl)tetrahydrofuran-3-yl)methanol (28.72 g) in DCM (150 mL), and the mixture was stirred at RT for 18 h. Sodium bicarbonate (sat., aq., 200 mL) was then added, the mixture extracted with EtOAc (3×300 mL), dried over MgSO4 and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (5% to 30% EtOAc in hexanes) to obtain the title compound (37.07 g). 1H-NMR (400 MHz, CDCl3) δ (ppm): 3.22 (dd, J=8.1, 4.5 Hz, 1 H), 3.31 (td, J=8.0, 3.0 Hz, 1 H), 3.94-4.07 (m, 1 H), 4.31-4.46 (m, 1 H), 4.53 (d, J=9.9 Hz, 1 H), 4.83 (d, J=9.9 Hz, 1 H), 6.97-7.14 (m, 1 H), 7.22 (td, J=7.7, 1.3 Hz, 1 H), 7.31-7.45 (m, 1 H), 7.49-7.61 (m, 2 H), 7.61-7.70 (m, 1 H), 7.75 (td, J=8.1, 1.5 Hz, 1 H), 7.79-7.93 (m, 2 H), 8.90 (s, 1 H), 11.85 (s, 1 H)

Workup

  1. extractionthe mixture extracted with EtOAc (3×300 mL)
  2. dry with materialdried over MgSO4
  3. concentrationconcentrated under reduced pressure
  4. customThe residue was purified by silica gel column chromatography (5% to 30% EtOAc in hexanes)

Sources & evidence

ORD record
ord-ebe0ffce09ad411090b0924213acf8cf
Source dataset
uspto-grants-2015_01
Patent number
US08940734B2

Reaction notes

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