Triethylamine → HCID 58180879, compound

HRID 1772844Notes

Reaction equation

HRID 1772844 reaction equation
C(N(CC)CC)C.[C:8]([C:10]1[CH:18]=[CH:17][C:13]([C:14]([OH:16])=O)=[C:12]([F:19])[CH:11]=1)#[N:9].F[P-](F)(F)(F)(F)F.C[N+](C)=C(N(C)C)ON1C2N=CC=CC=2N=N1.[OH:44][CH2:45][CH:46]1[NH:51][CH2:50][CH2:49][N:48]([C:52]([O:54][C:55]([CH3:58])([CH3:57])[CH3:56])=[O:53])[CH2:47]1>C1COCC1.O.C(OCC)(=O)C>[C:8]([C:10]1[CH:18]=[CH:17][C:13]([C:14]([N:51]2[CH2:50][CH2:49][N:48]([C:52]([O:54][C:55]([CH3:56])([CH3:57])[CH3:58])=[O:53])[CH2:47][CH:46]2[CH2:45][OH:44])=[O:16])=[C:12]([F:19])[CH:11]=1)#[N:9]

Participants

8

Reactant 4

HCID 8471TriethylamineHCID 5906594-Cyano-2-fluorobenzoic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 223865084-N-Boc-2-hydroxymethylpiperazine

Product 1

HCID 58180879HCID 58180879, compoundYield 78.6%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

Triethylamine (892 μL, 6.40 mmol) was added to a mixture of 4-cyano-2-fluorobenzoic acid (275 mg, 1.66 mmol, Alfa Aesar) and N,N,N′,N′-tetramethyl-O-(7-azabenzotriazol-1-yl)uronium hexafluorophosphate (580 mg, 1.52 mmol) in THF (13 mL). After stirring for 15 min, tert-butyl 3-(hydroxymethyl)piperazine-1-carboxylate (0.30 g, 1.4 mmol, racemic, AstaTech) was added. The reaction was stirred overnight. Ethyl acetate and water were added, the mixture shaken, and layers separated. The organic layer was washed with water, 0.1N NaOH, and brine; dried over sodium sulfate, decanted and concentrated. Flash chromatography on a 40 g silica gel cartridge, eluting with a gradient from 0-100% EtOAc in hexanes afforded the racemic product as a white solid (400 mg, 71%). 1H NMR (300 MHz, CDCl3): δ 7.61-7.38 (m, 3H), 4.90-2.51 (m, 9H), 1.47 (s, 9H); LCMS (M-tBu+2H)+: 308.1.

Workup

  1. stirringThe reaction was stirred overnight
  2. stirringthe mixture shaken
  3. customlayers separated
  4. washThe organic layer was washed with water, 0.1N NaOH, and brine
  5. dry with materialdried over sodium sulfate
  6. customdecanted
  7. concentrationconcentrated
  8. washFlash chromatography on a 40 g silica gel cartridge, eluting with a gradient from 0-100% EtOAc in hexanes

Sources & evidence

ORD record
ord-e87f640ab13f4b3f91e8621ebf6827bb
Source dataset
uspto-grants-2016_02
Patent number
US09249145B2

Reaction notes

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