Tetrabutylammonium Fluoride → HCID 86658430, compound

HRID 1968880Notes

Reaction equation

HRID 1968880 reaction equation
[Si]([O:8][C:9]1[CH:14]=[CH:13][C:12]([N:15]([CH2:27][C@@H:28]([NH:33][C:34](=[O:40])[O:35][C:36]([CH3:39])([CH3:38])[CH3:37])[C@@H:29]([CH3:32])[CH2:30][CH3:31])[C:16]([C@@H:18]2[CH2:20][C@H:19]2[C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][N:22]=2)=[O:17])=[CH:11][CH:10]=1)(C(C)(C)C)(C)C.[F-].C([N+](CCCC)(CCCC)CCCC)CCC>O1CCCC1>[OH:8][C:9]1[CH:14]=[CH:13][C:12]([N:15]([CH2:27][C@@H:28]([NH:33][C:34](=[O:40])[O:35][C:36]([CH3:37])([CH3:39])[CH3:38])[C@@H:29]([CH3:32])[CH2:30][CH3:31])[C:16]([C@@H:18]2[CH2:20][C@H:19]2[C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][N:22]=2)=[O:17])=[CH:11][CH:10]=1

Participants

4

Reactant 2

HCID 2724141Tetrabutylammonium FluorideHCID 86658429HCID 86658429, compound

Product 1

HCID 86658430HCID 86658430, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of tert-butyl (2S,3S)-1-(N-(4-(tert-butyldimethylsilyloxy)phenyl)-trans-2-(pyridin-2-yl)cyclopropanecarboxamido)-3-methylpentan-2-ylcarbamate (720 mg, 1.3 mmol) and tetrahydrofuran (25 mL) was treated with tetrabutylammonium fluoride (1 M THF solution, 2.5 mL, 2.5 mmol). The reaction was maintained at room temperature for 2 h, then concentrated under reduced pressure to afford an oil that was purified by column chromatography on silica gel (eluting with 40% ethyl acetate in hexanes) to afford a mixture of diastereomers that was purified by chiral chromatography [Column: ChiralPak AD-H 4.6×250 mm, 25% solvent B (60% Ethanol in hexane) in solvent A (hexane) isocratic, retention time: 6.08 min.] to afford tert-butyl (2S,3S)-1-((1R,2R)—N-(4-hydroxyphenyl)-2-(pyridin-2-yl)cyclopropanecarboxamido)-3-methylpentan-2-ylcarbamate as an oil: 1H NMR (300 MHz, CDCl3) δ 8.96 (br. s., 1H), 8.12 (d, J=4.8 Hz, 1H), 7.39 (t, J=7.7 Hz, 1H), 7.09 (d, J=7.8 Hz, 1H), 6.79-6.95 (m, 3H), 6.54 (d, J=8.4 Hz, 2H), 5.13 (d, J=9.2 Hz, 1H), 4.28 (t, J=12.8 Hz, 1H), 3.49-3.66 (m, 1H), 2.87 (dd, J=13.6, 3.7 Hz, 1H), 2.47-2.61 (m, 1H), 1.84-1.98 (m, 1H), 1.38-1.47 (m, 1H), 1.32 (s, 9H), 1.23-1.28 (m, 1H), 0.85-1.01 (m, 1H), 0.73 (d, J=6.9 Hz, 3H), 0.68 (t, J=7.4 Hz, 3H); LRMS (ESI) m/e 454.2 [(M+H)+, calcd for C26H36N3O4 454.3].

Workup

  1. concentrationconcentrated under reduced pressure
  2. customto afford an oil that
  3. customwas purified by column chromatography on silica gel (eluting with 40% ethyl acetate in hexanes)
  4. customto afford
  5. additiona mixture of diastereomers that
  6. customwas purified by chiral chromatography [Column: ChiralPak AD-H 4.6×250 mm, 25% solvent B (60% Ethanol in hexane) in solvent A (hexane) isocratic, retention time: 6.08 min.]

Sources & evidence

ORD record
ord-5b4772f2cafb4ad08ac277289cc1d1b1
Source dataset
uspto-grants-2013_04
Patent number
US08426414B2

Reaction notes

Loading…