Diisopropylethylamine → Tert-butyl-2-(1-(3,4-difluoro-2-(2-fluoro-4-iodophenylamino)benzoyl)-3-hydroxyazetidin-3-yl)cyclohexylcarbamate

HRID 1672936Notes

Reaction equation

HRID 1672936 reaction equation
[OH:1][C:2]1([CH:6]2[CH2:11][CH2:10][CH2:9][CH2:8][CH:7]2[NH:12][C:13](=[O:19])[O:14][C:15]([CH3:18])([CH3:17])[CH3:16])[CH2:5][NH:4][CH2:3]1.[F:20][C:21]1[C:22]([NH:31][C:32]2[CH:37]=[CH:36][C:35]([I:38])=[CH:34][C:33]=2[F:39])=[C:23]([CH:27]=[CH:28][C:29]=1[F:30])[C:24](F)=[O:25].C(N(CC)C(C)C)(C)C>O1CCCC1>[C:15]([O:14][C:13](=[O:19])[NH:12][CH:7]1[CH2:8][CH2:9][CH2:10][CH2:11][CH:6]1[C:2]1([OH:1])[CH2:3][N:4]([C:24](=[O:25])[C:23]2[CH:27]=[CH:28][C:29]([F:30])=[C:21]([F:20])[C:22]=2[NH:31][C:32]2[CH:37]=[CH:36][C:35]([I:38])=[CH:34][C:33]=2[F:39])[CH2:5]1)([CH3:16])([CH3:18])[CH3:17]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 594691583,4-Difluoro-2-(2-fluoro-4-iodoanilino)benzoyl fluorideHCID 67051547Tert-butyl 2-(3-hydroxyazetidin-3-yl)cyclohexylcarbamate

Product 1

HCID 86621268Tert-butyl-2-(1-(3,4-difluoro-2-(2-fluoro-4-iodophenylamino)benzoyl)-3-hydroxyazetidin-3-yl)cyclohexylcarbamate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
50 °C

Procedure

To a solution of tert-butyl 2-(3-hydroxyazetidin-3-yl)cyclohexylcarbamate (181 mg, 0.669 mmol) and 3,4-difluoro-2-(2-fluoro-4-iodophenylamino)benzoyl fluoride (265 mg, 0.669 mmol), prepared using procedures similar to those described in Reference 1, in tetrahydrofuran (2.2 mL) was added N,N-diisopropylethylamine (110 μL) at room temperature. After an hour, the reaction mixture was heated to 50° C. and stirred for 45 minutes, at which time it was cooled to room temperature and evaporated. The residue was partitioned between ethyl acetate and 10% citric acid. The organic layer was washed with aqueous sodium chloride, dried over anhydrous sodium sulfate, filtered and concentrated in vacuo to afford tert-butyl-2-(1-(3,4-difluoro-2-(2-fluoro-4-iodophenylamino)benzoyl)-3-hydroxyazetidin-3-yl)cyclohexylcarbamate. This crude material was taken into the next step without further purification.

Workup

  1. waitAfter an hour
  2. temperaturewas cooled to room temperature
  3. customevaporated
  4. customThe residue was partitioned between ethyl acetate and 10% citric acid
  5. washThe organic layer was washed with aqueous sodium chloride
  6. dry with materialdried over anhydrous sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-cdc14418e107401984f8c6389713d2f8
Source dataset
uspto-grants-2011_08
Patent number
US07999006B2

Reaction notes

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