Isopropylamine → 4-(3-Hydroxy-1-azetidinyl)-N-(1-methylethyl)benzamide

HRID 1049133Notes

Reaction equation

HRID 1049133 reaction equation
F[P-](F)(F)(F)(F)F.[N:8]1(O[P+](N(C)C)(N(C)C)N(C)C)[C:12]2[CH:13]=CC=C[C:11]=2N=N1.[OH:28][CH:29]1[CH2:32][N:31]([C:33]2[CH:41]=[CH:40][C:36]([C:37]([OH:39])=O)=[CH:35][CH:34]=2)[CH2:30]1.CC(N)C.C(N(CC)C(C)C)(C)C>ClCCl>[OH:28][CH:29]1[CH2:30][N:31]([C:33]2[CH:34]=[CH:35][C:36]([C:37]([NH:8][CH:12]([CH3:13])[CH3:11])=[O:39])=[CH:40][CH:41]=2)[CH2:32]1

Participants

6

Reactant 4

HCID 6363IsopropylamineHCID 81531DiisopropylethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 83818271HCID 83818271, compound

Product 1

HCID 711435344-(3-Hydroxy-1-azetidinyl)-N-(1-methylethyl)benzamideYield 94.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Benzotriazol-1-yloxytris(dimethylamino)phosphonium hexafluorophosphate (4.64 g, 10.5 mmol, from Aldrich) was added to a mixture of 4-(3-hydroxyazetidin-1-yl)benzoic acid (1.93 g, 10.0 mmol), 2-propanamine (4.26 mL, 50.0 mmol) and N,N-diisopropylethylamine (3.88 g, 30.0 mmol) in dichloromethylene (10 mL). The mixture was stirred at room temperature for 2 h, and diluted with dichloromethane. The mixture was washed with aqueous NaHCO3 and brine, dried over Na2SO4, filtered and concentrated under reduced pressure. The residue was purified by flash chromatography on a silica gel column eluting with ethyl acetate in hexane (gradient: 0-50%) to afford the desired product (2.21 g, 94.3%). LCMS cacld. for C13H19N2O2 (M+1)+: m/z=235.1. Found: 235.1.

Workup

  1. washThe mixture was washed with aqueous NaHCO3 and brine
  2. dry with materialdried over Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated under reduced pressure
  5. customThe residue was purified by flash chromatography on a silica gel column
  6. washeluting with ethyl acetate in hexane (gradient: 0-50%)

Sources & evidence

ORD record
ord-4c6b88eae32f4303b98d739f894d0c71
Source dataset
uspto-grants-2016_07
Patent number
US09382231B2

Reaction notes

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