Allyl bromide → N-((1S,3R)-3-(allyloxy)-6-methoxy-2,3-dihydro-1H-inden-1-yl)-2,2,2-trifluoroacetamide

HRID 501687Notes

Reaction equation

HRID 501687 reaction equation
[F:1][C:2]([F:19])([F:18])[C:3]([NH:5][C@@H:6]1[C:14]2[C:9](=[CH:10][CH:11]=[C:12]([O:15][CH3:16])[CH:13]=2)[C@H:8]([OH:17])[CH2:7]1)=[O:4].[Li][CH2:21][CH2:22][CH2:23]C.C(Br)C=C>C1COCC1>[CH2:23]([O:17][C@H:8]1[C:9]2[C:14](=[CH:13][C:12]([O:15][CH3:16])=[CH:11][CH:10]=2)[C@@H:6]([NH:5][C:3](=[O:4])[C:2]([F:18])([F:19])[F:1])[CH2:7]1)[CH:22]=[CH2:21]

Participants

5

Reactant 3

HCID 7841Allyl bromideHCID 596761532,2,2-trifluoro-N-((1S,3R)-3-hydroxy-6-methoxy-2,3-dihydro-1H-inden-1-yl)acetamideHCID 178418339Butyllithium

Product 1

HCID 58813111N-((1S,3R)-3-(allyloxy)-6-methoxy-2,3-dihydro-1H-inden-1-yl)-2,2,2-trifluoroacetamideYield 46%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

Step U (1): A solution of 2,2,2-trifluoro-N-((1S,3R)-3-hydroxy-6-methoxy-2,3-dihydro-1H-inden-1-yl)acetamide (enantiomer A, 2.65 g, 9.63 mmol) from step T (1) was cooled to −78° C. in THF. Added n-BuLi (7.7 mL, 19.3 mmol, 2.5M in Hex, Aldrich). Allowed the precipitous mixture to stir at −78° C. for 30 min. Added allyl bromide (4.6 mL, 48.2 mmol, Aldrich), warmed to rt and the reaction became homogeneous. The mixture was stirred for 18 h. Quenched with 1M HCl. Extracted with EtOAc. Washed with brine, dried over Na2SO4, filtered and concentrated. The residue was purified by silica gel column chromatography to afford 1.38 g (46% yield) of N-((1S,3R)-3-(allyloxy)-6-methoxy-2,3-dihydro-1H-inden-1-yl)-2,2,2-trifluoroacetamide as white solid. LC-MS (M+Na)+=337.9; [α]D −115.43 (c=6.79 mg/mL, dioxane); Anal. Calcd for C15H16F3NO3: C, 57.14; H, 5.11; N, 4.44. Found: C, 57.19; H, 4.88; N, 4.31. 1H NMR (500 MHz, CDCl3) δ ppm 1.55 (s, 2H) 2.09 (d, J=14.04 Hz, 1H) 2.61-2.73 (m, 1H) 3.80 (s, 2H) 4.06 (dd, J=3.05, 1.53 Hz, 2H) 4.79 (dd, J=5.49, 1.83 Hz, 1H) 5.19 (dd, J=10.53, 1.37 Hz, 1H) 5.28 (dd, J=17.24, 1.68 Hz, 1H) 5.39 (s, 1H) 5.83-5.97 (m, 1H) 6.85-6.98 (m, 2H) 7.32 (d, J=8.24 Hz, 1H).

Workup

  1. stirringThe mixture was stirred for 18 h
  2. customQuenched with 1M HCl
  3. extractionExtracted with EtOAc
  4. washWashed with brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-e8fe0be6c4824610b61c02a0e9442a56
Source dataset
uspto-grants-2010_08
Patent number
US07772221B2

Reaction notes

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