Boron trifluoride etherate → HCID 71715908, compound

HRID 1477549Notes

Reaction equation

HRID 1477549 reaction equation
[CH:1]1([CH2:7][N:8]2[CH2:12][C@@H:11]([NH:13][C:14]([C:16]3[CH:25]=[CH:24][C:23]4[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=4)[C:17]=3[OH:26])=[O:15])[CH2:10][C@H:9]2[C:27]([OH:29])=[O:28])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[C:30](OC(=N)C(Cl)(Cl)Cl)([CH3:33])([CH3:32])[CH3:31].B(F)(F)F.CCOCC>C1COCC1>[C:30]([O:28][C:27]([C@@H:9]1[CH2:10][C@H:11]([NH:13][C:14]([C:16]2[CH:25]=[CH:24][C:23]3[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=3)[C:17]=2[OH:26])=[O:15])[CH2:12][N:8]1[CH2:7][CH:1]1[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1)=[O:29])([CH3:33])([CH3:32])[CH3:31]

Participants

5

Reactant 3

HCID 8000Boron trifluoride etherateHCID 2734700Tert-butyl 2,2,2-trichloroethanimidateHCID 89768055HCID 89768055, compound

Product 1

HCID 71715908HCID 71715908, compoundYield 35%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

A mixture of (2S,4S)-1-cyclohexylmethyl-4-[(1-hydroxy-naphthalene-2-carbonyl)-amino]-pyrrolidine-2-carboxylic acid (50 mg, 0.13 mmol) and 2,2,2-trichloro-acetimidic acid tert-butyl ester (70 mg, 0.33 mmol) in THF (1 mL) was stirred at 0° C. for several minutes. Then BF3.OEt2 (20 mg, 0.13 mmol) was added dropwise at 0° C. and the reaction mixture was warmed to room temp. and stirred for 2 h. The reaction mixture was then quenched with brine solution, extracted with ethyl acetate and washed with water and brine. The organic layer was dried over anhydrous sodium sulfate, concentrated and purified by column chromatography (using 5% EtOAc in hexane as eluent) to give (2S,4S)-1-cyclohexylmethyl-4-[(1-hydroxy-naphthalene-2-carbonyl)-amino]-pyrrolidine-2-carboxylic acid tert-butyl ester (20 mg, 35.0% yield) as a bluish sticky liquid. MS calcd. for C27H37N2O4 [(M+H)+] 453.0, obsd. 453.2.

Workup

  1. temperaturethe reaction mixture was warmed to room temp.
  2. stirringstirred for 2 h
  3. customThe reaction mixture was then quenched with brine solution
  4. extractionextracted with ethyl acetate
  5. washwashed with water and brine
  6. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  7. concentrationconcentrated
  8. custompurified by column chromatography (using 5% EtOAc in hexane as eluent)

Sources & evidence

ORD record
ord-6b8c5f18fa8a4dc7b10f6172733fb10f
Source dataset
uspto-grants-2016_08
Patent number
US09403805B2

Reaction notes

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