Tetrahydrofuran → 3,4-Dimethyl-1-[(S)-3-(3-fluorophenyl)-4-(4-methoxyphenyl)butanoyl]-5-phenylimidazolidin-2-one

HRID 1816004Notes

Reaction equation

HRID 1816004 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([Mg]Br)=[CH:5][CH:4]=1.[CH2:11]1COCC1.[CH3:16][N:17]1[CH:21]([CH3:22])[CH:20]([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[N:19]([C:29](=[O:39])/[CH:30]=[CH:31]/[C:32]2[CH:37]=[CH:36][CH:35]=[C:34]([F:38])[CH:33]=2)[C:18]1=[O:40]>C1COCC1.C1(C)C=CC=CC=1.[Zn+2].[I-].[I-]>[CH3:16][N:17]1[CH:21]([CH3:22])[CH:20]([C:23]2[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=2)[N:19]([C:29](=[O:39])[CH2:30][C@@H:31]([C:32]2[CH:37]=[CH:36][CH:35]=[C:34]([F:38])[CH:33]=2)[CH2:11][C:6]2[CH:7]=[CH:8][C:3]([O:2][CH3:1])=[CH:4][CH:5]=2)[C:18]1=[O:40]

Participants

6

Reactant 3

HCID 8028TetrahydrofuranHCID 698141353,4-Dimethyl-1-[(E)-3-(3-fluorophenyl)prop-2-enoyl]-5-phenylimidazolidin-2-oneHCID 178491912HCID 178491912, compound

Product 1

HCID 698148773,4-Dimethyl-1-[(S)-3-(3-fluorophenyl)-4-(4-methoxyphenyl)butanoyl]-5-phenylimidazolidin-2-one

Reagents, catalysts & solvents 2

HCID 9883512zinc(II)iodideCatalystHCID 22635083Tetrahydrofuran tolueneSolvent

Conditions

Temperature
-20 °C

Procedure

A solution of 4-methoxyphenylmagnesium bromide in THF (0.31 M, 14.7 mL, 4.56 mmole) was added dropwise to a stirred suspension of (4 R, 5 S)-3,4-dimethyl-1-[(E)-3-(3-fluorophenyl)prop-2-enoyl]-5-phenylimidazolidin-2-one (514 mg, 1.52 mmole), CuBr.DMS complex (229 mg, 1.06 mmole), and ZnI2 (582 mg, 1.82 mmole) in THF/toluene (10 mL) at −15° C. After 1.5 hr the reaction was quenched with saturated NH4Cl and extracted with EtOAc (3×). The combined organic layers were dried over MgSO4 and concentrated to dryness. The residue was taken up in 1:1 Et2O/hexanes and cooled at −20° C. for 18 hr. The solid was collected, washed with 1: Et2O/hexanes, and dried in vacuum to afford a first crop of the title compound. The filtrate was concentrated and the residue was purified by flash chromatography on silica gel (30% EtOAc/hexanes) to afford additional title compound as a yellow oil that solidified in vacuum. The total yield of the title compound was 0.62 g(91%): 1HNMR (300 MHz, CDCl3) δ 6.75-7.37 (m, 13 H), 5.10 (d, J=8.5 Hz, 1 H), 3.80 (s, 3 H), 3.65-3.85 (m, 1 H), 3.63 (dd, J=16.7, 9.6 Hz, 1 H), 3.36-3.41 (m, 1H), 3.14 (dd, J=16.7, 4.9 Hz, 1 H), 2.72-2.88 (m, 2 H), 2.79 (s, 3 H), 0.74 (d, J=6.6 Hz, 3 H).

Workup

  1. customat −15° C
  2. customAfter 1.5 hr the reaction was quenched with saturated NH4Cl
  3. extractionextracted with EtOAc (3×)
  4. dry with materialThe combined organic layers were dried over MgSO4
  5. concentrationconcentrated to dryness
  6. customThe solid was collected
  7. washwashed with 1
  8. dry with materialEt2O/hexanes, and dried in vacuum

Sources & evidence

ORD record
ord-f66121316a9c414babd80dc741c24d65
Source dataset
uspto-grants-2005_04
Patent number
US06881736B1

Reaction notes

Loading…