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

HRID 68383Notes

Reaction equation

HRID 68383 reaction equation
[NH2:1][C@@:2]1([C:10]2[CH:15]=[CH:14][C:13]([F:16])=[CH:12][C:11]=2[F:17])[CH2:6][O:5][C@H:4]([CH3:7])[C@H:3]1[CH2:8][OH:9].[C:18]([N:26]=[C:27]=[S:28])(=[O:25])[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1>C(Cl)Cl>[F:17][C:11]1[CH:12]=[C:13]([F:16])[CH:14]=[CH:15][C:10]=1[C@@:2]1([NH:1][C:27]([NH:26][C:18](=[O:25])[C:19]2[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=2)=[S:28])[C@H:3]([CH2:8][OH:9])[C@@H:4]([CH3:7])[O:5][CH2:6]1

Participants

4

Reactant 2

HCID 68284Benzoyl isothiocyanateHCID 68296354((2R*,3R*,4S*)-4-Amino-4-(2,4-difluorophenyl)-2-methyltetrahydrofuran-3-yl)methanol

Product 1

HCID 86707822N-(((3S*,4R*,5R*)-3-(2,4-Difluorophenyl)-4-(hydroxymethyl)-5-methyltetrahydrofuran-3-yl)carbamothioyl)benzamideYield 82.8%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

((2R*,3R*,4S*)-4-Amino-4-(2,4-difluorophenyl)-2-methyltetrahydrofuran-3-yl)methanol (120 mg, 0.49 mmol) was dissolved in DCM (2 mL). Benzoyl isothiocyanate (66 μl, 0.49 mmol) was added and the reaction was stirred at room temperature for 30 minutes. The reaction mixture was concentrated in vacuo and purified by column chromatography, eluting with 0-30% EtOAc in n-hexane to leave the title compound as a yellow oil (165 mg). 1H NMR (400 MHz, CDCl3) δ ppm: 11.81 (s, 1H), 8.89 (s, 1H), 7.84-7.91 (m, 2H), 7.62-7.75 (m, 2H), 7.49-7.58 (m, 2H), 6.91 (dt, J=1.71, 8.38 Hz, 1H), 6.80 (ddd, J=2.63, 8.80, 11.80 Hz, 1H), 4.69 (d, J=10.15 Hz, 1H), 4.39 (dd, J=1.71, 10.15 Hz, 1H), 3.91-4.08 (m, 3H), 2.85 (dd, J=4.58, 6.79 Hz, 1H), 2.59 (dt, J=3.73, 8.10 Hz, 1H), 1.37 (d, J=5.99 Hz, 3H).

Workup

  1. concentrationThe reaction mixture was concentrated in vacuo
  2. custompurified by column chromatography
  3. washeluting with 0-30% EtOAc in n-hexane

Sources & evidence

ORD record
ord-8a590a1885d94e74b561a116b1cd2a2f
Source dataset
uspto-grants-2014_09
Patent number
US08822455B2

Reaction notes

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