Trifluoroacetic acid → HCID 90457072, compound

HRID 625879Notes

Reaction equation

HRID 625879 reaction equation
[Br:1][C:2]1[C:3]([O:12][C@H:13]2[CH2:17][NH:16][C@H:15]([C:18]([OH:20])=[O:19])[CH2:14]2)=[N:4][C:5]2[C:10]([CH:11]=1)=[CH:9][CH:8]=[CH:7][CH:6]=2.C(O)(C(F)(F)F)=O.C(=O)([O-])[O-].[K+].[K+].[C:34](Cl)(=[O:50])[O:35][CH2:36][CH:37]1[C:49]2[CH:48]=[CH:47][CH:46]=[CH:45][C:44]=2[C:43]2[C:38]1=[CH:39][CH:40]=[CH:41][CH:42]=2>O1CCOCC1.O>[CH:48]1[C:49]2[CH:37]([CH2:36][O:35][C:34]([N:16]3[CH2:17][C@H:13]([O:12][C:3]4[C:2]([Br:1])=[CH:11][C:10]5[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=5)[N:4]=4)[CH2:14][C@H:15]3[C:18]([OH:20])=[O:19])=[O:50])[C:38]3[C:43](=[CH:42][CH:41]=[CH:40][CH:39]=3)[C:44]=2[CH:45]=[CH:46][CH:47]=1

Participants

7

Reactant 4

HCID 6422Trifluoroacetic acidHCID 11430Potassium CarbonateHCID 343679-Fluorenylmethyl chloroformateHCID 90456612HCID 90456612, compound

Product 1

HCID 90457072HCID 90457072, compoundYield 65%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 312751,4-DioxaneSolvent

Procedure

To a solution of (2S,4R)-4-((3-bromoquinolin-2-yl)oxy)pyrrolidine-2-carboxylic acid, TFA (310 mg, 0.687 mmol) in 1,4-dioxane (3 mL) and water (12 mL) was added potassium carbonate (380 mg, 2.75 mmol) followed by (9H-fluoren-9-yl)methyl carbonochloridate (178 mg, 0.687 mmol) at 0° C. The mixture was stirred at RT for 18 hrs and treated with water (10 ml). The resulting mixture was extracted with diethyl ether (2×15 ml). The aqueous phase was acidified with aq. HCl (1M) to pH 2-3, and extracted with DCM (3×20 ml). The combined organic layers were dried over MgSO4 and concentrated to give the crude product. The crude product was purified via prep HPLC (10-100% CH3CN:Water, 0.1% TFA buffer) to afford the product (2S,4R)-1-(((9H-fluoren-9-yl)methoxy)carbonyl)-4-((3-bromoquinolin-2-yl)oxy)pyrrolidine-2-carboxylic acid (250 mg, 65% yield) as a white solid. 1H NMR (500 MHz, methanol-d4) d 7.90-7.75 (m, 2H), 7.73-7.63 (m, 2H), 7.58-7.49 (m, 2H), 7.49-7.39 (m, 2H), 7.37-7.31 (m, 1H), 7.26 (t, J=7.5 Hz, 1H), 7.20-7.14 (m, 1H), 7.12 (t, J=7.4 Hz, 1H), 7.04 (td, J=7.4, 1.0 Hz, 1H), 4.68-4.56 (m, 2H), 4.51 (t, J=8.3 Hz, 1H), 4.44-4.33 (m, 2H), 4.27-4.16 (m, 2H), 3.99-3.92 (m, 1H), 3.81-3.73 (m, 1H), 3.73-3.64 (m, 1H). ESI-MS(+) m/z=337 (M+H).

Workup

  1. extractionThe resulting mixture was extracted with diethyl ether (2×15 ml)
  2. extractionextracted with DCM (3×20 ml)
  3. dry with materialThe combined organic layers were dried over MgSO4
  4. concentrationconcentrated
  5. customto give the crude product
  6. customThe crude product was purified via prep HPLC (10-100% CH3CN:Water, 0.1% TFA buffer)

Sources & evidence

ORD record
ord-67176f0b22284b2089568fa4fc961f69
Source dataset
uspto-grants-2016_04
Patent number
US09308236B2

Reaction notes

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