Tetrabutylammonium Fluoride → HCID 68283978, compound

HRID 1527580Notes

Reaction equation

HRID 1527580 reaction equation
[Cl:1][C:2]1[C:3]([F:45])=[C:4]([CH:42]=[CH:43][CH:44]=1)[CH2:5][NH:6][C:7]([C@@H:9]1[CH2:13][C@@H:12]([F:14])[CH2:11][N:10]1[C:15](=[O:41])[CH2:16][N:17]1[C:25]2[C:20](=[CH:21][CH:22]=[C:23]([CH2:26][O:27][Si](C(C)C)(C(C)C)C(C)C)[CH:24]=2)[C:19]([C:38](=[O:40])[CH3:39])=[CH:18]1)=[O:8].CCCC[N+](CCCC)(CCCC)CCCC.[F-]>C1COCC1>[Cl:1][C:2]1[C:3]([F:45])=[C:4]([CH:42]=[CH:43][CH:44]=1)[CH2:5][NH:6][C:7]([C@@H:9]1[CH2:13][C@@H:12]([F:14])[CH2:11][N:10]1[C:15](=[O:41])[CH2:16][N:17]1[C:25]2[C:20](=[CH:21][CH:22]=[C:23]([CH2:26][OH:27])[CH:24]=2)[C:19]([C:38](=[O:40])[CH3:39])=[CH:18]1)=[O:8]

Participants

4

Reactant 2

HCID 2724141Tetrabutylammonium FluorideHCID 68283985HCID 68283985, compound

Product 1

HCID 68283978HCID 68283978, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of (2S,4R)-1-[2-(3-acetyl-6-triisopropylsilanyloxymethyl-indol-1-yl)-acetyl]-4-fluoro-pyrrolidine-2-carboxylic acid 3-chloro-2-fluoro-benzylamide (50.0 mg, 0.057 mmol) in THF (5 mL), cooled to at 0° C., was added TBAF (1M in THF, 0.057 mL, 0.057 mmol), and stirring was continued for 3 h. The reaction was quenched with saturated aqueous NaHCO3 followed by addition of EtOAc. The layers were separated and the aqueous phase was extracted with EtOAc. The combined organics were washed with water (1×) and brine, dried (phase separator) and concentrated in vacuo. Purification by preparative HPLC (Waters Sunfire, C18-ODB, 5 μm, 30×100 mm, flow: 40 mL/min, eluent: 20% CH3CN/H2O/20 min, 100% CH3CN/2 min, CH3CN and H2O containing 0.1% TFA) afforded after lyophilization of the purified fractions the title compound as a white solid. MS (LC/MS): 504 [M+H]+; tR (HPLC conditions k): 3.10 min.

Workup

  1. customThe reaction was quenched with saturated aqueous NaHCO3
  2. additionfollowed by addition of EtOAc
  3. customThe layers were separated
  4. extractionthe aqueous phase was extracted with EtOAc
  5. washThe combined organics were washed with water (1×) and brine
  6. customdried (phase separator)
  7. concentrationconcentrated in vacuo
  8. customPurification by preparative HPLC (Waters Sunfire, C18-ODB, 5 μm, 30×100 mm, flow: 40 mL/min, eluent: 20% CH3CN/H2O/20 min, 100% CH3CN/2 min, CH3CN and H2O containing 0.1% TFA)

Sources & evidence

ORD record
ord-1cf619cb162a4d97b0fa8d5a1d73c0c3
Source dataset
uspto-grants-2015_07
Patent number
US09085555B2

Reaction notes

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