Cyclopentyl Isocyanate → HCID 16113992, compound

HRID 1874146Notes

Reaction equation

HRID 1874146 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([C:17]2[CH:22]=[C:21]([C:23]([F:26])([F:25])[F:24])[CH:20]=[C:19]([F:27])[CH:18]=2)([NH2:16])[CH2:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)=[CH:4][C:3]=1[C:28]([F:31])([F:30])[F:29].[CH:32]1([N:37]=[C:38]=[O:39])[CH2:36][CH2:35][CH2:34][CH2:33]1>O1CCOCC1>[CH:32]1([NH:37][C:38]([NH:16][C:8]([C:5]2[CH:6]=[CH:7][C:2]([F:1])=[C:3]([C:28]([F:31])([F:29])[F:30])[CH:4]=2)([C:17]2[CH:22]=[C:21]([C:23]([F:24])([F:25])[F:26])[CH:20]=[C:19]([F:27])[CH:18]=2)[CH2:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)=[O:39])[CH2:36][CH2:35][CH2:34][CH2:33]1

Participants

4

Reactant 2

HCID 643500Cyclopentyl IsocyanateHCID 248285091-(4-Fluoro-3-(trifluoromethyl)phenyl)-1-(3-fluoro-5-(trifluoromethyl)phenyl)-2-phenylethanamine

Product 1

HCID 16113992HCID 16113992, compoundYield 67%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

1-(4-Fluoro-3-(trifluoromethyl)phenyl)-1-(3-fluoro-5-(trifluoromethyl)phenyl)-2-phenylethanamine (300 mg, 0.67 mmol) and cyclopentyl isocyanate (0.4 mL, 5.3 eq) were stirred in 1,4-dioxane (2 mL) at room temperature overnight. The reaction mixture was concentrated, and purified by flash chromatography (silica gel, hexanes/EtOAc) to give the racemic mixture of 1-cyclopentyl-3-(1-(4-fluoro-3-(trifluoromethyl)phenyl)-1-(3-fluoro-5-(trifluoromethyl)phenyl)-2-phenylethyl)urea (250 mg, yield: 67%). The racemate (250 mg) was dissolved in 10% isopropanol in heptane, and was resolved by chiral prep HPLC using an AD column (10% isopropanol/heptane/0.1% DEA, isocratic) to give the fast eluting enantiomer 1 (110 mg) corresponding to (5)-1-cyclopentyl-3-(1-(4-fluoro-3-(trifluoromethyl)phenyl)-1-(3-fluoro-5-(trifluoromethyl)phenyl)-2-phenylethyl)urea, (analytical chiral HPLC (AD, 10% isopropanol/heptane/0.1% DEA, isocratic), retention time=4.85 min) and the slow eluting enantiomer 2 (105 mg) corresponding to (R)-1-cyclopentyl-3-(1-(4-fluoro-3-(trifluoromethyl)phenyl)-1-(3-fluoro-5-(trifluoromethyl)phenyl)-2-phenylethyl)urea, (analytical chiral HPLC (AD, 10% isopropanol/heptane/0.1% DEA, isocratic), retention time=14.11 min) LCMS (10-90% MeOH in H2O with 0.1% TFA in a 4-min run), retention time=4.33 min, 557.32 (M+H); 1H NMR (400 MHz, CDCl3) δ ppm 7.36-7.44 (m, 2H), 7.23-7.29 (m, 3H), 7.13-7.21 (m, 4H), 6.68-6.74 (m, 2H), 4.84 (s, 1H), 4.40 (s, br, 1H), 3.84-3.95 (m, 3H), 1.88-1.98 (m, 2H), 1.56-1.68 (m, 4H), 1.34 (d, J=6.36 Hz, 2 H).

Workup

  1. concentrationThe reaction mixture was concentrated
  2. custompurified by flash chromatography (silica gel, hexanes/EtOAc)
  3. customto give

Sources & evidence

ORD record
ord-b8dba6111d1e4cd6abbaaca680f01db0
Source dataset
uspto-grants-2012_11
Patent number
US08304403B2

Reaction notes

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