o-Xylyl bromide → (3S)-3-[4-(2-Methyl-benzyloxy)-phenyl]-hex-4-ynoic acid methyl ester

HRID 1160279Notes

Reaction equation

HRID 1160279 reaction equation
[CH3:1][C:2]1[CH:9]=[CH:8][CH:7]=[CH:6][C:3]=1[CH2:4]Br.[CH3:10][O:11][C:12](=[O:25])[CH2:13][C@@H:14]([C:18]1[CH:23]=[CH:22][C:21]([OH:24])=[CH:20][CH:19]=1)[C:15]#[C:16][CH3:17].C([O-])([O-])=O.[Cs+].[Cs+]>CC(C)=O>[CH3:10][O:11][C:12](=[O:25])[CH2:13][C@@H:14]([C:18]1[CH:19]=[CH:20][C:21]([O:24][CH2:4][C:3]2[CH:6]=[CH:7][CH:8]=[CH:9][C:2]=2[CH3:1])=[CH:22][CH:23]=1)[C:15]#[C:16][CH3:17]

Participants

5

Reactant 3

HCID 6992o-Xylyl bromideHCID 10796Cesium carbonateHCID 59855119(3S)-3-(4-Hydroxy-phenyl)-hex-4-ynoic acid methyl ester

Product 1

HCID 68676002(3S)-3-[4-(2-Methyl-benzyloxy)-phenyl]-hex-4-ynoic acid methyl ester

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent

Procedure

2-Methylbenzyl bromide (0.98 g, 5.3 mmol) and phenol 1 (0.97 g, 4.4 mmol) were dissolved in acetone (9 mL) and treated with Cs2CO3 (1.45 g, 4.4 mmol). The reaction was stirred at room temperature for 16 h then filtered and concentrated to an oil which was purified by radial chromatography (2 mm silica gel plate, 10% ethyl acetate in hexanes). Eluant containing compound 13.1 was concentrated to a colorless oil (1.37 g, 96%). This material was analyzed by chiral HPLC (Daicel ChiralPAK AD-H column, eluant: 0.1% TFA in 95:5 hexanes:2-propanol) and was found to have 94% ee. 1H NMR(500 MHz)(MeOH-d4) δ 7.39 (d, 1H, J=7 Hz); 7.28 (d, 2H, J=8.5 Hz); 7.25-7.15 (m, 3H); 5.05 (s, 2H); 4.02 (m, 1H); 3.64 (s, 3H); 2.68 (m, 2H); 2.36 (s, 3H); 1.80 (d, 3H, J=2.5 Hz). MS ESI (pos.) m/e: 323.0 (M+H); 245.1 (M+Na).

Workup

  1. filtrationthen filtered
  2. concentrationconcentrated to an oil which
  3. customwas purified by radial chromatography (2 mm silica gel plate, 10% ethyl acetate in hexanes)
  4. additionEluant containing compound 13.1
  5. concentrationwas concentrated to a colorless oil (1.37 g, 96%)

Sources & evidence

ORD record
ord-9f4c812d83d24d3397404d967f36e2f6
Source dataset
uspto-grants-2010_10
Patent number
US07816367B2

Reaction notes

Loading…