Lithium Hydroxide → HCID 56592629, compound

HRID 2359262Notes

Reaction equation

HRID 2359262 reaction equation
[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]

Participants

10

Reactant 4

HCID 3939Lithium HydroxideHCID 72879MethanesulfonamideHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 66767258Benzoic acid, 5-chloro-4-[4-chloro-2-(difluoromethoxy)phenoxy]-2-fluoro-, ethyl ester

Product 1

HCID 56592629HCID 56592629, compoundYield 25.4%

Reagents, catalysts & solvents 5

HCID 142844-(Dimethylamino)pyridineCatalystHCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

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).

Workup

  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

Sources & evidence

ORD record
ord-78af4621493c4a5f8acef0699eb59d58
Source dataset
uspto-grants-2014_04
Patent number
US08685977B2

Reaction notes

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