Benzoyl isothiocyanate → N-(((3S,4R,5S)-3-(2,4-difluorophenyl)-4-(hydroxymethyl)-5-((trityloxy)methyl)tetrahydrofuran-3-yl)carbamothioyl)benzamide

HRID 68373Notes

Reaction equation

HRID 68373 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:41]2[CH:46]=[CH:45][C:44]([F:47])=[CH:43][C:42]=2[F:48])[CH2:17][O:16][C@H:15]([CH2:18][O:19][C:20]([C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=2)([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[C@H:14]1[CH2:39][OH:40]>C(Cl)Cl>[F:48][C:42]1[CH:43]=[C:44]([F:47])[CH:45]=[CH:46][C:41]=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]([CH2:39][OH:40])[C@@H:15]([CH2:18][O:19][C:20]([C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=2)([C:21]2[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=2)[C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[O:16][CH2:17]1

Participants

4

Reactant 2

HCID 68284Benzoyl isothiocyanateHCID 86707812((2S,3R,4S)-4-Amino-4-(2,4-difluorophenyl)-2-((trityloxy)methyl)tetrahydrofuran-3-yl)methanol

Product 1

HCID 86707813N-(((3S,4R,5S)-3-(2,4-difluorophenyl)-4-(hydroxymethyl)-5-((trityloxy)methyl)tetrahydrofuran-3-yl)carbamothioyl)benzamideYield 96.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Benzoyl isothiocyanate (1.24 mL, 9.2 mmol) was added to a stirred solution of ((2S,3R,4S)-4-amino-4-(2,4-difluorophenyl)-2-((trityloxy)methyl)tetrahydrofuran-3-yl)methanol (4.2 g, 8.4 mmol) in dry DCM (20 mL) at RT under nitrogen. After 1 hour the volatiles were removed in vacuo and then the residue was purified by column chromatography (normal phase, 100 g, Biotage SNAP cartridge KP-Sil, 50 mL per min, gradient 5% to 30% EtOAc in n-hexane) to give the title compound (5.4 g). 1H NMR (400 MHz, MeOH-d4) δ ppm: 2.71-2.83 (m, 1 H) 3.12 (dd, J=10.15, 4.52 Hz, 1 H) 3.27 (dd, J=10.15, 3.67 Hz, 1 H) 3.83 (d, J=5.26 Hz, 2 H) 4.19-4.27 (m, 1 H) 4.55 (d, J=9.78 Hz, 1 H) 5.18 (d, J=9.78 Hz, 1 H) 6.82-6.96 (m, 2 H) 7.17-7.32 (m, 9 H) 7.36-7.41 (m, 6 H) 7.49-7.57 (m, 3 H) 7.60-7.67 (m, 1 H) 7.89-7.94 (m, 2 H),

Workup

  1. customAfter 1 hour the volatiles were removed in vacuo
  2. customthe residue was purified by column chromatography (normal phase, 100 g, Biotage SNAP cartridge KP-Sil, 50 mL per min, gradient 5% to 30% EtOAc in n-hexane)

Sources & evidence

ORD record
ord-f441d59e7d4146a5800ab8ba4c9ddfd4
Source dataset
uspto-grants-2014_09
Patent number
US08822455B2

Reaction notes

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