Diisopropylethylamine → (S)-2-[(4-Cyano-2,6-difluorophenylamino)-methyl]-piperidine-1-carboxylic acid tert-butyl ester

HRID 2074404Notes

Reaction equation

HRID 2074404 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH2:11][CH2:10][C@H:9]1[CH2:14][NH2:15])=[O:7])([CH3:4])([CH3:3])[CH3:2].[F:16][C:17]1[CH:18]=[C:19]([CH:22]=[C:23]([F:26])[C:24]=1F)[C:20]#[N:21].C(N(C(C)C)CC)(C)C>C1(C)C(C)=CC=CC=1>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH2:11][CH2:10][C@H:9]1[CH2:14][NH:15][C:24]1[C:17]([F:16])=[CH:18][C:19]([C:20]#[N:21])=[CH:22][C:23]=1[F:26])=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 5938143,4,5-TrifluorobenzonitrileHCID 1502020tert-Butyl (2S)-2-(aminomethyl)piperidine-1-carboxylate

Product 1

HCID 67090562(S)-2-[(4-Cyano-2,6-difluorophenylamino)-methyl]-piperidine-1-carboxylic acid tert-butyl esterYield 7.2%

Reagents, catalysts & solvents 1

HCID 7237O-XyleneSolvent

Procedure

(S)-2-Aminomethyl-piperidine-1-carboxylic acid tert-butyl ester (1.36 g) and 3,4,5-trifluorobenzonitrile (1.00 g) were heated under argon in xylene (10 ml) containing diisopropylethylamine (3.3 ml) for 16 h. The reaction mixture was cooled and partitioned between ethyl acetate and water. The organic phase was washed with brine, dried and evaporated to give a solid which was triturated with pentane-ether to afford the title product (0.16 g) as an off white powder. Chromatography of the mother liquors on silica gel eluting with ethyl acetate-pentane mixtures afforded further title product (0.92 g). Mass Spectrum (API+): Found 252 (MH+−tBoc). C18H23F2N3O2 requires 351.

Workup

  1. temperatureThe reaction mixture was cooled
  2. custompartitioned between ethyl acetate and water
  3. washThe organic phase was washed with brine
  4. customdried
  5. customevaporated
  6. customto give a solid which
  7. customwas triturated with pentane-ether

Sources & evidence

ORD record
ord-78ad3920a93c4a2c85715ea00e594a1a
Source dataset
uspto-grants-2011_04
Patent number
US07919507B2

Reaction notes

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