1-Iodo-2-methoxyethane → 1-[2-(tert-Butoxycarbonyl)-4-methoxybutyl]cyclopentanecarboxylic acid

HRID 22909

反応式

HRID 22909 の反応式
C([N-]C(C)C)(C)C.[Li+].[C:9]([O:13][C:14](=[O:25])[CH2:15][CH2:16][C:17]1([C:22]([OH:24])=[O:23])[CH2:21][CH2:20][CH2:19][CH2:18]1)([CH3:12])([CH3:11])[CH3:10].[CH3:26][O:27][CH2:28][CH2:29]I>O1CCCC1.CCCCCCC.C(C1C=CC=CC=1)C.COCCOC.CCCCCCC>[C:9]([O:13][C:14]([CH:15]([CH2:29][CH2:28][O:27][CH3:26])[CH2:16][C:17]1([C:22]([OH:24])=[O:23])[CH2:21][CH2:20][CH2:19][CH2:18]1)=[O:25])([CH3:12])([CH3:10])[CH3:11]

参加物

7

反応物 3

HCID 791361-Iodo-2-methoxyethaneHCID 2724682Lithium diisopropylamideHCID 11010130t-Butyl 3-(1-carboxycyclopentyl)propanoate

生成物 1

HCID 113585031-[2-(tert-Butoxycarbonyl)-4-methoxybutyl]cyclopentanecarboxylic acid収率 81%

試薬・触媒・溶媒 3

HCID 80711,2-Dimethoxyethane溶媒3 回HCID 8900Heptane溶媒HCID 22742125Tetrahydrofuran heptane ethylbenzol溶媒

反応条件

温度
-10 °C

実験手順

To a solution of commercially supplied lithium diisopropylamide (9.63 kg of a 2M solution in tetrahydrofuran/n-heptane/ethylbenzene, 23.7 mol) in 1,2-dimethoxyethane (25 L) at −10° C. under an atmosphere of N2 was added a solution of 1-(3-tert-butoxy-3-oxopropyl)cyclopentane carboxylic acid (EP274234B1—see Example 35) (2.5 kg, 10.3 mol) in 1,2-dimethoxyethane (12.5 L) with stirring over a period of 4 hours whilst maintaining the reaction temperature at −10° C. The header tank was washed with 1,2-dimethoxyethane (2.5 L) and this was added to the reaction. The reaction mixture was then allowed to stir at −10° C. for 1.75 hours. To the resultant solution was added a solution of 2-iodoethyl methyl ether (2.73 kg, 14.4 mol) in 1,2-dimethoxyethane (10 L) over a period of 1.75 hours. The reaction was then stirred at this temperature for 4 hours before warming to 20° C. over a period of 4 hours. After stirring at this temperature for 8 hours the reaction was quenched by the addition of aqueous ammonium chloride (25 L of a 2.8 M solution), ethyl acetate (12.5 L) was then added. Aqueous hydrochloric acid (10 L of 5 M solution) was then added with stirring to adjust the pH to between 2 and 3. The two phases were mixed and then separated. The organic phase was then extracted three times with aqueous potassium carbonate solution (0.3 M solution; 37.5 L, 12.5 L and then 6.25 L). To the combined aqueous phases was then added n-heptane (15.6 L), and aqueous hydrochloric acid (14.5 L of a 5 M solution) with stirring until the pH of the aqueous layer was between 2 and 3. The layers were then separated and the aqueous phase was extracted with n-heptane (15.6 L). The combined organic phases were then washed with saturated brine (3.1 L) and were then concentrated under vacuum to give the crude title compound (2.50 kg, 8.32 mol, 81% yield) as a solution in n-heptane (21.8 kg total solution weight).

後処理

  1. washThe header tank was washed with 1,2-dimethoxyethane (2.5 L)
  2. additionthis was added to the reaction
  3. stirringto stir at −10° C. for 1.75 hours
  4. stirringThe reaction was then stirred at this temperature for 4 hours
  5. temperaturebefore warming to 20° C. over a period of 4 hours
  6. stirringAfter stirring at this temperature for 8 hours the reaction
  7. customwas quenched by the addition of aqueous ammonium chloride (25 L of a 2.8 M solution), ethyl acetate (12.5 L)
  8. additionwas then added
  9. additionAqueous hydrochloric acid (10 L of 5 M solution) was then added
  10. stirringwith stirring
  11. additionThe two phases were mixed
  12. customseparated
  13. extractionThe organic phase was then extracted three times with aqueous potassium carbonate solution (0.3 M solution
  14. stirringadded n-heptane (15.6 L), and aqueous hydrochloric acid (14.5 L of a 5 M solution) with stirring until the pH of the aqueous layer
  15. customThe layers were then separated
  16. extractionthe aqueous phase was extracted with n-heptane (15.6 L)
  17. washThe combined organic phases were then washed with saturated brine (3.1 L)
  18. concentrationwere then concentrated under vacuum

出典と根拠

ORDレコード
ord-94e0c045f0b0471a843a5ca1f0170d63
出典データセット
uspto-grants-2005_02
特許番号
US06849649B2

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