Trifluoroacetic anhydride → HCID 11201679, compound

HRID 1713341Notes

Reaction equation

HRID 1713341 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([CH:7]=[C:8]([CH3:32])[C:9]=1[C:10]#[C:11][CH2:12][C:13]([CH2:19][C:20]1([CH3:31])[C:29]2[C:24](=[CH:25][CH:26]=[C:27]([F:30])[CH:28]=2)[O:23][CH2:22][CH2:21]1)([OH:18])[C:14]([F:17])([F:16])[F:15])[C:5]#[N:6].FC(F)(F)C(OC(=O)C(F)(F)F)=O.CN(C)C(=N)N(C)C>ClCCl>[CH3:32][C:8]1[CH:7]=[C:4]([C:5]#[N:6])[CH:3]=[C:2]2[C:9]=1[CH:10]=[C:11]([CH2:12][C:13]([CH2:19][C:20]1([CH3:31])[C:29]3[C:24](=[CH:25][CH:26]=[C:27]([F:30])[CH:28]=3)[O:23][CH2:22][CH2:21]1)([OH:18])[C:14]([F:15])([F:16])[F:17])[NH:1]2

Participants

5

Reactant 3

HCID 9845Trifluoroacetic anhydrideHCID 664601,1,3,3-TetramethylguanidineHCID 68639193HCID 68639193, compound

Product 1

HCID 11201679HCID 11201679, compoundYield 17%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
140 °C

Procedure

To a chilled (0° C.) solution of 500 mg (1.1 mmol) of 3-amino-5-methyl-4-[5,5,5-trifluoro-4-(6-fluoro-4-methylchroman-4-ylmethyl)-4-hydroxypent-1-ynyl]benzonitrile in 20 mL of dichloromethane was added 460 μL (3.3 mmol) of trifluoroacetic anhydride. After 15 minutes, the reaction was concentrated in vacuo and the residue three times diluted with ether and concentrated. The resulting oil was dissolved in 1.5 mL of DMSO, and then 0.4 mL (3.2 mmol) of tetramethylguanidine was added and the mixture was warmed at 140° C. in a microwave oven. After 10 minutes, the mixture was cooled and poured onto crushed ice. The resulting solid was collected by filtration, air dried, and chromatographed on silica gel eluting with ethyl acetate-hexanes (gradient: 0-30% EtOAc) to afford two diastereomers. Further purification of the separated diastereomers by preparatory TLC (silica gel, ethyl acetate-hexanes (7:3)) gave first 82 mg (17%) of the title compound as a single diastereomer (M−1=445) and second 80 mg (17%) of the title compound as the opposite diastereomer (M−1=445).

Workup

  1. concentrationthe reaction was concentrated in vacuo
  2. additionthe residue three times diluted with ether
  3. concentrationconcentrated
  4. dissolutionThe resulting oil was dissolved in 1.5 mL of DMSO
  5. waitAfter 10 minutes
  6. temperaturethe mixture was cooled
  7. additionpoured
  8. customonto crushed ice
  9. filtrationThe resulting solid was collected by filtration, air
  10. customdried
  11. customchromatographed on silica gel eluting with ethyl acetate-hexanes (gradient: 0-30% EtOAc)
  12. customto afford two diastereomers
  13. customFurther purification of the separated diastereomers by preparatory TLC (silica gel, ethyl acetate-hexanes (7:3))

Sources & evidence

ORD record
ord-1403bb4021ba4814a9f9226090dc07c4
Source dataset
uspto-grants-2010_09
Patent number
US07795272B2

Reaction notes

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