Lithium Hydroxide → HCID 56592629、化合物

HRID 2359262ノート

反応式

HRID 2359262 の反応式
[Cl:1][C:2]1[C:3]([O:14][C:15]2[CH:20]=[CH:19][C:18]([Cl:21])=[CH:17][C:16]=2[O:22][CH:23]([F:25])[F:24])=[CH:4][C:5]([F:13])=[C:6]([CH:12]=1)[C:7](OCC)=[O:8].[OH-].[Li+].Cl.CN(C)CCCN=C=NCC.[CH3:40][S:41]([NH2:44])(=[O:43])=[O:42]>O1CCCC1.O.C(OCC)(=O)C.CN(C)C1C=CN=CC=1.ClCCl>[Cl:1][C:2]1[C:3]([O:14][C:15]2[CH:20]=[CH:19][C:18]([Cl:21])=[CH:17][C:16]=2[O:22][CH:23]([F:25])[F:24])=[CH:4][C:5]([F:13])=[C:6]([CH:12]=1)[C:7]([NH:44][S:41]([CH3:40])(=[O:43])=[O:42])=[O:8]

参加物

10

反応物 4

HCID 3939Lithium HydroxideHCID 72879MethanesulfonamideHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 66767258Ethyl 5-chloro-4-[4-chloro-2-(difluoromethoxy)phenoxy]-2-fluorobenzoate

生成物 1

HCID 56592629HCID 56592629、化合物収率 25.4%

試薬・触媒・溶媒 5

HCID 142844-(Dimethylamino)pyridine触媒HCID 962Water溶媒HCID 6344Dichloromethane溶媒HCID 8028Tetrahydrofuran溶媒HCID 8857Ethyl Acetate溶媒

実験手順

To a solution of ethyl 5-chloro-4-[4-chloro-2-(difluoromethoxy)phenoxy]-2-fluorobenzoate (Preparation 131, 0.070 g, 0.000177 mol) in tetrahydrofuran (2.50 mL) and water (2.50 mL) was added lithium hydroxide (0.050 g, 0.00209 mol). The reaction mixture was stirred at room temperature under nitrogen for 4 hours. The reaction was diluted with ethyl acetate (10.0 mL) and washed with a saturated aqueous solution of brine (10.0 mL). The organic layer was separated, dried with sodium sulphate, filtered and concentrated in vacuo. The crude was taken up in dichloromethane (5.0 mL) and N-[3-(dimethylamino)propyl]-N′-ethylcarbodiimide hydrochloride (0.051 g, 0.000266 mol), N,N-dimethylpyridin-4-amine (0.049 g, 0.000401) and methanesulfonamide (0.026 g, 0.000273 mol) were added and the mixture was stirred at room temperature under nitrogen for 16 hours. The reaction was diluted in dichloromethane (10.0 mL) and washed twice with an aqueous solution of hydrochloric acid (2M, 15.0 mL). The biphasic system was passed through a separation cartridge to collect the organic layer, which was then concentrated in vacuo. The crude was purified using silica gel column chromatography eluting with 0-100% EtOAc in heptane, 4 g. The compound obtained was then triturated in tert-butyl methyl ether to yield title compound as a pale pink solid (0.020 g, 25% yield).

後処理

  1. washwashed with a saturated aqueous solution of brine (10.0 mL)
  2. customThe organic layer was separated
  3. dry with materialdried with sodium sulphate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. stirringthe mixture was stirred at room temperature under nitrogen for 16 hours
  7. washwashed twice with an aqueous solution of hydrochloric acid (2M, 15.0 mL)
  8. customto collect the organic layer, which
  9. concentrationwas then concentrated in vacuo
  10. customThe crude was purified
  11. washeluting with 0-100% EtOAc in heptane, 4 g
  12. customThe compound obtained
  13. customwas then triturated in tert-butyl methyl ether

出典と根拠

ORDレコード
ord-78af4621493c4a5f8acef0699eb59d58
出典データセット
uspto-grants-2014_04
特許番号
US08685977B2

反応ノート

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