Methoxyacetic Acid → HCID 89600721, compound

HRID 1021305Notes

Reaction equation

HRID 1021305 reaction equation
[Si]([O:8][CH2:9][C:10]1[C:11]([F:26])=[C:12]([N:16]2[CH2:19][CH:18]([CH:20]3[CH2:25][CH2:24][NH:23][CH2:22][CH2:21]3)[CH2:17]2)[CH:13]=[CH:14][CH:15]=1)(C(C)(C)C)(C)C.[CH3:27][O:28][CH2:29][C:30](O)=O.CCN=C=NCCCN(C)C.Cl.C1C=CC2N(O)N=NC=2C=1.[OH-].[Na+]>C(Cl)(Cl)Cl.ClCCl>[F:26][C:11]1[C:10]([CH2:9][OH:8])=[CH:15][CH:14]=[CH:13][C:12]=1[N:16]1[CH2:17][CH:18]([CH:20]2[CH2:21][CH2:22][N:23]([CH2:30][CH2:29][O:28][CH3:27])[CH2:24][CH2:25]2)[CH2:19]1

Participants

8

Reactant 5

HCID 12251Methoxyacetic AcidHCID 14798Sodium HydroxideHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 86686244HCID 86686244, compound

Product 1

HCID 89600721HCID 89600721, compoundYield 103.7%

Reagents, catalysts & solvents 2

HCID 6212ChloroformSolventHCID 6344DichloromethaneSolvent

Procedure

4-{1-[3-({[tert-butyl(dimethyl)silyl]oxy}methyl)-2-fluorophenyl]azetidin-3-yl}piperidine (120 mg) and methoxy acetic acid (47 mg) was mixed with dichloromethane (3 ml), and WSC hydrochloride (100 mg) and HOBt (70 mg) was added thereto, followed by stirring at room temperature for 3 hours. A 1 M aqueous NaOH solution and CHCl3 were added to the reaction mixture, and the organic layer was dried over Na2SO4 and concentrated under reduced pressure. The obtained residue was mixed with THF (3 ml), and a 1 M TBAF/THF solution (0.66 ml) was added thereto, followed by stirring at room temperature for 1 hour. EtOAc and a saturated aqueous ammonium chloride solution were added to the reaction mixture, and the organic layer was dried over Na2SO4 and concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (hexane/EtOAc) to obtain 1-(4-{1-[2-fluoro-3-(hydroxymethyl)phenyl]azetidin-3-yl}piperidin-1-yl)-2-methoxyethan one (106 mg).

Workup

  1. additionwas added
  2. dry with materialthe organic layer was dried over Na2SO4
  3. concentrationconcentrated under reduced pressure
  4. additionThe obtained residue was mixed with THF (3 ml)
  5. additiona 1 M TBAF/THF solution (0.66 ml) was added
  6. stirringby stirring at room temperature for 1 hour
  7. additionEtOAc and a saturated aqueous ammonium chloride solution were added to the reaction mixture
  8. dry with materialthe organic layer was dried over Na2SO4
  9. concentrationconcentrated under reduced pressure
  10. customThe obtained residue was purified by silica gel column chromatography (hexane/EtOAc)

Sources & evidence

ORD record
ord-dbd88b699a014511926385d613e61cfc
Source dataset
uspto-grants-2014_05
Patent number
US08716470B2

Reaction notes

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