Methoxyacetic Acid → HCID 68310292, compound

HRID 2171705Notes

Reaction equation

HRID 2171705 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:31].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[CH2:19][CH:18]([CH:20]2[CH2:25][CH2:24][N:23]([C:30](=[O:31])[CH2:29][O:28][CH3:27])[CH2:22][CH2:21]2)[CH2:17]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 68310292HCID 68310292, compoundYield 99.4%

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 1M 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 1M 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-methoxyethanone (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 1M 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-bf63935d16124bacb8e49a2ddb8cb5a6
Source dataset
uspto-grants-2015_06
Patent number
US09051283B2

Reaction notes

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