3-Bromo-2-methyl-1-propene → 2-(3,5-Bis-benzyloxyphenyl)-4-methyl-pent-4-enoic acid methyl ester

HRID 599132Notes

Reaction equation

HRID 599132 reaction equation
[Li+].CC([N-]C(C)C)C.C1COCC1.CCCCCCC.[CH2:21]([C:23]1[CH:28]=CC=C[CH:24]=1)C.[CH3:29][O:30][C:31](=[O:55])[CH2:32][C:33]1[CH:38]=[C:37]([O:39][CH2:40][C:41]2[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=2)[CH:36]=[C:35]([O:47][CH2:48][C:49]2[CH:54]=[CH:53][CH:52]=[CH:51][CH:50]=2)[CH:34]=1.BrCC(C)=C>C1COCC1>[CH3:29][O:30][C:31](=[O:55])[CH:32]([C:33]1[CH:34]=[C:35]([O:47][CH2:48][C:49]2[CH:54]=[CH:53][CH:52]=[CH:51][CH:50]=2)[CH:36]=[C:37]([O:39][CH2:40][C:41]2[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=2)[CH:38]=1)[CH2:24][C:23]([CH3:28])=[CH2:21]

Participants

6

Reactant 4

HCID 3577853-Bromo-2-methyl-1-propeneHCID 640121Methyl [3,5-bis(benzyloxy)phenyl]acetateHCID 2724682Lithium diisopropylamideHCID 22742125Tetrahydrofuran heptane ethylbenzol

Product 1

HCID 577550392-(3,5-Bis-benzyloxyphenyl)-4-methyl-pent-4-enoic acid methyl esterYield 94.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

A 2M solution of LDA in THF-heptane-ethylbenzene (21.5 mL, 43.0 mmol) was added dropwise over 12 min to a stirred solution of (3,5-bis-benzyloxyphenyl)acetic acid methyl ester (prepared in Example 1, step (a)) (13.0 g, 35.9 mmol) in THF (80 mL) at −78° C. under a nitrogen atmosphere. The temperature was maintained below −70° C. for an additional 50 min, then 3-bromo-2-methylpropene (4.0 mL, 39.7 mmol) was added in one portion and the reaction mixture was warmed to 0° C. After 2 h the mixture was concentrated in vacuo, diluted with sat. aq. NH4Cl (100 mL) and extracted with EtOAc (100 mL). The organic layer was washed with brine (100 mL), dried (MgSO4), concentrated in vacuo and purified by flash chromatography (silica, 0-10% EtOAc in petroleum ether) to afford the title product as a yellow oil (14.1 g, 94%). 1H-NMR (400 MHz, CDCl3): δ7.42-7.25 (m, 10H), 6.58 (s, 2H), 6.52 (s, 1H), 5.02 (s, 4H), 4.74 (s, 1H), 4.66 (s, 1H), 3.74 (t, 1H), 3.64 (s, 3H), 2.79 (dd, 1H), 2.38 (dd, 1H), 1.70 (s, 3H).

Workup

  1. temperatureThe temperature was maintained below −70° C. for an additional 50 min
  2. concentrationAfter 2 h the mixture was concentrated in vacuo
  3. additiondiluted with sat. aq. NH4Cl (100 mL)
  4. extractionextracted with EtOAc (100 mL)
  5. washThe organic layer was washed with brine (100 mL)
  6. dry with materialdried (MgSO4)
  7. concentrationconcentrated in vacuo
  8. custompurified by flash chromatography (silica, 0-10% EtOAc in petroleum ether)

Sources & evidence

ORD record
ord-657032952091493ab75a315038521ffb
Source dataset
uspto-grants-2011_03
Patent number
US07897643B2

Reaction notes

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