Hexane → 1-((4S)-5,5-Dimethyl-4-vinyl(1,3-dioxan-2-yl))-4-methoxybenzene

HRID 1919403Notes

Reaction equation

HRID 1919403 reaction equation
[Li][CH2:2]CCC.CCCCCC.[CH3:12][O:13][C:14]1[CH:19]=[CH:18][C:17]([CH:20]2[O:25][C@@H:24]([CH:26]=O)[C:23]([CH3:29])([CH3:28])[CH2:22][O:21]2)=[CH:16][CH:15]=1>[Br-].C[P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.O1CCCC1>[CH3:29][C:23]1([CH3:28])[CH2:22][O:21][CH:20]([C:17]2[CH:16]=[CH:15][C:14]([O:13][CH3:12])=[CH:19][CH:18]=2)[O:25][C@H:24]1[CH:26]=[CH2:2]

Participants

6

Reactant 3

HCID 8058HexaneHCID 86628867(4R)-2-(4-Methoxyphenyl)-5,5-dimethyl-1,3-dioxan-4-carbaldehydeHCID 178418339Butyllithium

Product 1

HCID 673497541-((4S)-5,5-Dimethyl-4-vinyl(1,3-dioxan-2-yl))-4-methoxybenzeneYield 81%

Reagents, catalysts & solvents 2

HCID 74505Methyltriphenyliphosphonium bromideCatalystHCID 8028TetrahydrofuranSolvent

Procedure

Following the general procedure for the methylenation by Wittig-olefination of Description 8, a phosphorous ylide generated from 73.4 g (205.5 mmol) of methyltriphenylphosphonium bromide and 125.7 mL of 1.6 M n-BuLi in hexane (201.1 mmol) in 440 mL of anhydrous tetrahydrofuran (THF), was reacted with 25.0 g (100.0 mmol) of (4R)-2-(4-methoxyphenyl)-5,5-dimethyl-1,3-dioxan-4-carbaldehyde (8b). Aqueous work-up followed by purification using column chromatography with mixtures of diethyl ether (Et2O), ethyl acetate (EtOAc), and hexanes (Hxn) as eluent (Et2O/Hxn=1:25→EtOAc/Hxn=1:9) provided 20.0 g (81% yield) of the title compound (8c) as a yellow liquid. Rf=0.42 (MTBE/Hxn=1:9). 1H NMR (400 MHz, CHCl3): δ=0.81 (s, 3H), 1.15 (s, 3H), 3.65 (d, J=10.8 Hz, 1H), 3.76 (d, J=11.2 Hz, 1H), 3.81 (s, 3H), 4.03 (d, J=6.4 Hz, 1H), 5.23-527 (m, 1H), 5.29-5.35 (m, 1H), 5.50 (s, 1H), 5.86 (ddd, J=17.2, 10.8, 6.4 Hz, 1H), 6.87-6.92 (m, 2H), 7.43-7.48 (m, 2H) ppm. MS (ESI) m/z: 249.1 (M+H)+. The analytical data was consistent with the proposed structure and with the data given in the literature for the compound (Blakemore, et al., J. Org. Chem. 2005, 70, 5449-5460; and Shiina, et al., Bull Chem. Soc. Jpn. 2001, 74, 113-122).

Workup

  1. customAqueous work-up followed by purification

Sources & evidence

ORD record
ord-68221cff25514a6d97e0a5700cb763fd
Source dataset
uspto-grants-2012_05
Patent number
US08168617B2

Reaction notes

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