Methoxyacetic Acid → 1-[1-(Diphenylmethyl)azetidin-3-yl]-4-(methoxyacetyl)-piperazine

HRID 2063313Notes

Reaction equation

HRID 2063313 reaction equation
[C:1]1([CH:7]([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[N:8]2[CH2:11][CH:10]([N:12]3[CH2:17][CH2:16][NH:15][CH2:14][CH2:13]3)[CH2:9]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH3:24][O:25][CH2:26][C:27](O)=[O:28].CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F>CN(C=O)C>[C:18]1([CH:7]([C:1]2[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=2)[N:8]2[CH2:9][CH:10]([N:12]3[CH2:17][CH2:16][N:15]([C:27](=[O:28])[CH2:26][O:25][CH3:24])[CH2:14][CH2:13]3)[CH2:11]2)[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1

Participants

6

Reactant 4

HCID 12251Methoxyacetic AcidHCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 16123292HCID 16123292, compound

Product 1

HCID 161245951-[1-(Diphenylmethyl)azetidin-3-yl]-4-(methoxyacetyl)-piperazineYield 80.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 1-[1-(diphenylmethyl)azetidin-3-yl]piperazine (see Method 7a; 615 mg, 2.0 mmol) in DMF (8 mL) were added methoxy acetic acid (272 mg, 3.0 mmol), DIPEA (310 mg, 2.4 mmol) and TBTU (770 mg, 2.4 mmol). The reaction mixture was stirred at RT for 12 h and then partitioned between methylene chloride and aqueous NaHCO3. The aqueous phase was extracted twice with methylene chloride and then the combined organic solutions were washed with brine and dried over MgSO4. The solvent was removed by evaporation and the product was purified by means of reversed phase chromatography is using a mixture of acetonitrile and aqueous 0.1 M ammonium acetate as eluent. There was obtained 610 mg (80%) of 1-[1-(diphenylmethyl)azetidin-3-yl]-4-(methoxyacetyl)-piperazine. 1H NMR (500 MHz, CD3OD): 2.3-2.4 (m, 4H), 3.0 (m, 3H), 3.4 (s, 3H), 3.4 m, 2H), 3.5 (m, 2H), 3.6 (m, 2H), 4.1 (s, 2H), 4.5 (s, 1H), 7.2 (t, 2H), 7.3 (t, 4H), 7.4 (d, 41-1); LCMS: m/z 380 (M+1)+.

Workup

  1. custompartitioned between methylene chloride and aqueous NaHCO3
  2. extractionThe aqueous phase was extracted twice with methylene chloride
  3. washthe combined organic solutions were washed with brine
  4. dry with materialdried over MgSO4
  5. customThe solvent was removed by evaporation
  6. customthe product was purified by means of reversed phase chromatography
  7. additiona mixture of acetonitrile and aqueous 0.1 M ammonium acetate as eluent

Sources & evidence

ORD record
ord-3af394cec3de4c6aac4f468904998e52
Source dataset
uspto-grants-2012_10
Patent number
US08288370B2

Reaction notes

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