Lithium Hexamethyldisilazide → Methyl 4-{2-(3-bromophenyl)-3-[(4-methoxybenzyl)oxy]-1-methyl-3-oxopropyl}benzoate

HRID 2246892Notes

Reaction equation

HRID 2246892 reaction equation
[Li+].C[Si]([N-][Si](C)(C)C)(C)C.[Br:11][C:12]1[CH:13]=[C:14]([CH2:18][C:19]([O:21][CH2:22][C:23]2[CH:28]=[CH:27][C:26]([O:29][CH3:30])=[CH:25][CH:24]=2)=[O:20])[CH:15]=[CH:16][CH:17]=1.Br[CH:32]([C:34]1[CH:43]=[CH:42][C:37]([C:38]([O:40][CH3:41])=[O:39])=[CH:36][CH:35]=1)[CH3:33]>C1COCC1>[Br:11][C:12]1[CH:13]=[C:14]([CH:18]([C:19]([O:21][CH2:22][C:23]2[CH:24]=[CH:25][C:26]([O:29][CH3:30])=[CH:27][CH:28]=2)=[O:20])[CH:32]([C:34]2[CH:43]=[CH:42][C:37]([C:38]([O:40][CH3:41])=[O:39])=[CH:36][CH:35]=2)[CH3:33])[CH:15]=[CH:16][CH:17]=1

Participants

5

Reactant 3

HCID 2733832Lithium HexamethyldisilazideHCID 12342351Methyl 4-(1-bromoethyl)benzoateHCID 866195534-Methoxybenzyl (3-bromophenyl)acetate

Product 1

HCID 67262891Methyl 4-{2-(3-bromophenyl)-3-[(4-methoxybenzyl)oxy]-1-methyl-3-oxopropyl}benzoate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

LHMDS (1.0M THF, 2.6 mL) was added dropwise to a −78° C. THF (4 mL) solution containing the intermediate from Step A (0.827 g, 2.47 mmol). After stirring 10 minutes a THF (4 mL) solution containing methyl 4-(1-bromoethyl)benzoate (0.6 g, 2.47 mmol) was added dropwise. The solution was allowed to warm to room temperature. After 1.5 hours the solution was partitioned between ethyl acetate and aqueous 1N HCl. The organic phase was washed with water, brine and dried over magnesium sulfate. The solution was filtered and the residue purified by silica gel chromatography using a hexanes/ethyl acetate gradient to give the title compounds as a 1.67/1 mixture of diastereomers. 1H NMR (400 MHz, CDCl3): selected data δ 5.16 (d, J=12.0 Hz); 5.01 (d, J=12.0 Hz); 4.82 (d, J=12.0 Hz); 4.64 (d, J=11.9 Hz); 1.34 (d, J=6.8 Hz); 1.02 (d, J=7.0 Hz). Minor diastereomer: LCMS1 4.08 min (M+Na)=519. Major diastereomer: LC1 4.19 min (M+Na)=519.

Workup

  1. additionwas added dropwise
  2. customAfter 1.5 hours the solution was partitioned between ethyl acetate and aqueous 1N HCl
  3. washThe organic phase was washed with water, brine
  4. dry with materialdried over magnesium sulfate
  5. filtrationThe solution was filtered
  6. customthe residue purified by silica gel chromatography

Sources & evidence

ORD record
ord-107f6785369f41f9b2d38efe4db22efd
Source dataset
uspto-grants-2010_03
Patent number
US07687534B2

Reaction notes

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