Diisopropylethylamine → (Z)-1-(3,3-difluoroazetidin-1-yl)-3-iodoprop-2-en-1-one

HRID 1486966Notes

Reaction equation

HRID 1486966 reaction equation
[I:1]/[CH:2]=[CH:3]\[C:4]([OH:6])=O.CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.Cl.[F:41][C:42]1([F:46])[CH2:45][NH:44][CH2:43]1>C(Cl)Cl>[F:41][C:42]1([F:46])[CH2:45][N:44]([C:4](=[O:6])/[CH:3]=[CH:2]\[I:1])[CH2:43]1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 643796(Z)-3-Iodoacrylic acidHCID 27582473,3-Difluoroazetidine hydrochlorideHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)

Product 1

HCID 86730374(Z)-1-(3,3-difluoroazetidin-1-yl)-3-iodoprop-2-en-1-oneYield 49.8%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

A solution of (Z)-3-iodoacrylic acid (1a) (2.75 g, 1.0 eq.) in CH2Cl2 (25.0 mL) was cooled to 0° C. and sequentially treated with DIPEA (1.96 g, 1.1 eq), HATU (5.78 g, 1.1 eq) and 3,3-difluoroazetidine hydrochloride (1.98 g, 1.1 eq). The reaction mixture was stirred at 0° C. for 2-3 hr before being filtered, and concentrated under reduced pressure affording 3.5 g of crude compound. Purification by column chromatography (silica gel, elution with EtOAc/hexane) afforded 1.89 g of pure desired compound. Yield (49.87%). Mass: (ES+) 273.8 (M+1).

Workup

  1. filtrationbefore being filtered
  2. concentrationconcentrated under reduced pressure
  3. customaffording 3.5 g of crude compound
  4. customPurification
  5. washby column chromatography (silica gel, elution with EtOAc/hexane)

Sources & evidence

ORD record
ord-cb050a921dbc41f799ab93e480343a97
Source dataset
uspto-grants-2016_08
Patent number
US09428490B2

Reaction notes

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