Lithium Hexamethyldisilazide → 7-{1-[2-(4-methoxycarbonyl-phenyl)-vinyl]-hexyl}-4,4-dimethyl-3,4-dihydro-2H-quinoline-1-carboxylic acid tert-butyl ester

HRID 2415200Notes

Reaction equation

HRID 2415200 reaction equation
[CH3:1][O:2][C:3](=[O:17])[C:4]1[CH:9]=[CH:8][C:7]([CH2:10]P(OC)(OC)=O)=[CH:6][CH:5]=1.C[Si]([N-][Si](C)(C)C)(C)C.[Li+].[C:28]([O:32][C:33]([N:35]1[C:44]2[C:39](=[CH:40][CH:41]=[C:42]([CH:45]([CH:51]=O)[CH2:46][CH2:47][CH2:48][CH2:49][CH3:50])[CH:43]=2)[C:38]([CH3:54])([CH3:53])[CH2:37][CH2:36]1)=[O:34])([CH3:31])([CH3:30])[CH3:29]>C1COCC1>[C:28]([O:32][C:33]([N:35]1[C:44]2[C:39](=[CH:40][CH:41]=[C:42]([CH:45]([CH:51]=[CH:10][C:7]3[CH:6]=[CH:5][C:4]([C:3]([O:2][CH3:1])=[O:17])=[CH:9][CH:8]=3)[CH2:46][CH2:47][CH2:48][CH2:49][CH3:50])[CH:43]=2)[C:38]([CH3:53])([CH3:54])[CH2:37][CH2:36]1)=[O:34])([CH3:31])([CH3:30])[CH3:29]

Participants

5

Reactant 3

HCID 2733832Lithium HexamethyldisilazideHCID 108011704-(Dimethoxy-phosphorylmethyl)-benzoic acid methyl esterHCID 865890267-(1-formyl-hexyl)-4,4-dimethyl-3,4-dihydro-2H-quinoline-1-carboxylic acid tert-butyl ester

Product 1

HCID 692180957-{1-[2-(4-methoxycarbonyl-phenyl)-vinyl]-hexyl}-4,4-dimethyl-3,4-dihydro-2H-quinoline-1-carboxylic acid tert-butyl esterYield 80.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-20 °C

Procedure

A solution of 4-(dimethoxyphosphorylmethyl)-benzoic acid methyl ester (0.94 g, 3.6 mmole) in 10 mL of THF at −20° C., was treated with 3.7 mL of 1M lithium bis(trimethylsilyl)amide solution in hexanes. After 20 minutes at −20° C. a solution of 7-(1-formyl-hexyl)-4,4-dimethyl-3,4-dihydro-2H-quinoline-1-carboxylic acid tert-butyl ester (0.91 g, 2.4 mmole) in 5 mL of THF was added. The reaction mixture was stirred at −20° C. for 30 minutes, at room temperature for 6 hours, quenched by the addition of 10 mL of saturated aqueous ammonium chloride solution and extracted with three 10 mL portions of ethyl acetate. The combined organic extracts were dried over MgSO4, filtered and concentrated in vacuo to give a yellow oil. The product was purified by flash chromatography (SiO2, 5% ethyl acetate in hexanes) to yield 0.98 g of 7-{1-[2-(4-methoxycarbonyl-phenyl)-vinyl]-hexyl}-4,4-dimethyl-3,4-dihydro-2H-quinoline-1-carboxylic acid tert-butyl ester as a pale yellow oil.

Workup

  1. customquenched by the addition of 10 mL of saturated aqueous ammonium chloride solution
  2. extractionextracted with three 10 mL portions of ethyl acetate
  3. dry with materialThe combined organic extracts were dried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customto give a yellow oil
  7. customThe product was purified by flash chromatography (SiO2, 5% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-eb4ddb14f69e4112b644d80f2564ee53
Source dataset
uspto-grants-2004_11
Patent number
US06818652B2

Reaction notes

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