Diisopropylethylamine → 1,1-Dimethylethyl (2S)-2-[[[2-(4-bromophenyl)-2-oxoethyl]amino]carbonyl]-4,4-difluoro-1-pyrrolidinecarboxylate

HRID 709357Notes

Reaction equation

HRID 709357 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:12][C:11]([F:14])([F:13])[CH2:10][C@H:9]1[C:15]([OH:17])=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.Cl.[NH2:43][CH2:44][C:45]([C:47]1[CH:52]=[CH:51][C:50]([Br:53])=[CH:49][CH:48]=1)=[O:46].CCN(C(C)C)C(C)C>[Cl-].[Na+].O.O.CN(C=O)C>[C:1]([O:5][C:6]([N:8]1[CH2:12][C:11]([F:13])([F:14])[CH2:10][C@H:9]1[C:15](=[O:17])[NH:43][CH2:44][C:45]([C:47]1[CH:52]=[CH:51][C:50]([Br:53])=[CH:49][CH:48]=1)=[O:46])=[O:7])([CH3:2])([CH3:3])[CH3:4]

Participants

8

Reactant 4

HCID 81531DiisopropylethylamineHCID 27982162-Amino-1-(4-bromophenyl)ethan-1-one hydrochlorideHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 22977458(2S)-1-[(tert-butoxy)carbonyl]-4,4-difluoropyrrolidine-2-carboxylic acid

Product 1

HCID 591663481,1-Dimethylethyl (2S)-2-[[[2-(4-bromophenyl)-2-oxoethyl]amino]carbonyl]-4,4-difluoro-1-pyrrolidinecarboxylate

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
23 °C

Procedure

In a 50 mL pear-shaped flask, (S)-1-(tert-butoxycarbonyl)-4,4-difluoropyrrolidine-2-carboxylic acid (1 g, 3.98 mmol, Eq: 1.00) and HATU (1.51 g, 3.98 mmol, Eq: 1.00) were combined with DMF (15 ml) to give a colorless solution and stirred at 23° C. for 10 min. 2-Amino-1-(4-bromophenyl)ethanone HCl (995 mg, 3.98 mmol) was added followed by drop wise addition of DIPEA (1.54 g, 2.09 ml, 11.9 mmol). The suspension became a orange solution once the addition of the amine was completed. It was stirred at room temperature for 1 hr and diluted with brine (100 ml) and H2O (50 ml). The precipitate was filtered, washed with H2O and dried to afford (S)-tert-butyl2-(2-(4-bromophenyl)-2-oxoethylcarbamoyl)-4,4-difluoropyrrolidine-1-carboxylate as a light yellow solid. (1.8 g, >96%): ESI-LRMS m/e calcd for C18H21BrF2N2O4 [M+] 447. found 448 [M+H+].

Workup

  1. customto give a colorless solution
  2. stirringIt was stirred at room temperature for 1 hr
  3. filtrationThe precipitate was filtered
  4. washwashed with H2O
  5. customdried

Sources & evidence

ORD record
ord-eb9d4f8976e14155b2fbbab9e1ceedff
Source dataset
uspto-grants-2015_11
Patent number
US09180193B2

Reaction notes

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