(S)-N-benzhydryl-2-(3-(3,5-bis(trifluoromethyl)phenyl)thioureido)-N,3,3-trimethylbutanamide → (R)-4-((benzhydrylamino) (cyano)methyl)benzonitrile

HRID 537375Notes

Reaction equation

HRID 537375 reaction equation
[CH:1](/[N:14]=[CH:15]/[C:16]1[CH:23]=[CH:22][C:19]([C:20]#[N:21])=[CH:18][CH:17]=1)([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH:24]([N:37](C)C(=O)[C@@H](NC(NC1C=C(C(F)(F)F)C=C(C(F)(F)F)C=1)=S)C(C)(C)C)(C1C=CC=CC=1)C1C=CC=CC=1>>[CH:1]([NH:14][C@@H:15]([C:24]#[N:37])[C:16]1[CH:17]=[CH:18][C:19]([C:20]#[N:21])=[CH:22][CH:23]=1)([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

3

Reactant 2

HCID 44477827(S)-N-benzhydryl-2-(3-(3,5-bis(trifluoromethyl)phenyl)thioureido)-N,3,3-trimethylbutanamideHCID 178509840HCID 178509840, compound

Product 1

HCID 71293880(R)-4-((benzhydrylamino) (cyano)methyl)benzonitrileYield 96%

Procedure

The reaction was run at 0° C. for 20 h with stirring using (E)-4-((benzhydrylimino)methyl)benzonitrile (296 mg, 1.0 mmol, 1.0 equiv) and 10 mol % of (S)—N-benzhydryl-2-(3-(3,5-bis(trifluoromethyl)phenyl)thioureido)-N,3,3-trimethyl butanamide (4e). The product was subjected to purification by flash column chromatography (9:1, hexanes:Et2O) to afford (R)-4-((benzhydrylamino) (cyano)methyl)benzonitrile (310 mg, 0.96 mmol, 96% yield) as a white solid. The enantiomeric excess was determined to be 93% by chiral HPLC analysis (OD-H, 5.0% IPA in hexanes, 1.0 mL/min, 230 nm, tR(major)=41.1 min, tR(minor)=56.4 min); [α]D24=+27.3° (c=1.0, CHCl3). 1H NMR (500 MHz, CDCl3): δ 7.72 (4H, s), 7.57 (2H, d, J=7.5 Hz), 7.45 (2H, d, J=7.5 Hz), 7.39 (2H, t, J=7.8 Hz), 7.29-7.34 (3H, m), 7.23-7.27 (1H, m), 5.25 (1H, s), 4.67 (1H, br s), 2.25 (1H, br s). 13C {1H} NMR (125 MHz, CDCl3): δ 142.2, 140.5, 139.7, 132.7, 129.1, 128.8, 128.2, 128.0, 127.9, 127.4, 127.0, 118.1, 117.7, 113.1, 65.7, 52.0. IR (cm−1): 3310 (m), 3296 (m), 3025 (w), 2925 (w), 2845 (w), 2232 (m), 1609 (w), 1492 (m), 1453 (m), 1349 (m), 1189 (m), 925 (m), 746 (s), 703 (s).

Workup

  1. customThe product was subjected to purification by flash column chromatography (9:1, hexanes:Et2O)

Sources & evidence

ORD record
ord-8b8651b74d284f73aed288a2a87a2ffc
Source dataset
uspto-grants-2014_10
Patent number
US08859812B2

Reaction notes

Loading…