Hydrochloric Acid → (8-Benzyl-10-vinyl-11-oxa-3,8-diazaspiro[5.5]undecan-3-yl)-(4-isopropoxy-3-methyl-phenyl)methanone

HRID 73030Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 73030
[CH2:1]([N:8]1[CH2:25][CH:24]([CH:26]=[CH2:27])[O:23][C:10]2([CH2:15][CH2:14][N:13](C(OC(C)(C)C)=O)[CH2:12][CH2:11]2)[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl.[CH:29]([O:32][C:33]1[CH:41]=[CH:40][C:36]([C:37]([OH:39])=O)=[CH:35][C:34]=1[CH3:42])([CH3:31])[CH3:30].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(CC)CC)C>C(O)C.CN(C=O)C>[CH2:1]([N:8]1[CH2:25][CH:24]([CH:26]=[CH2:27])[O:23][C:10]2([CH2:11][CH2:12][N:13]([C:37]([C:36]3[CH:40]=[CH:41][C:33]([O:32][CH:29]([CH3:30])[CH3:31])=[C:34]([CH3:42])[CH:35]=3)=[O:39])[CH2:14][CH2:15]2)[CH2:9]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Komponenten

8

Edukt 5

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 592729354-Isopropoxy-3-methylbenzoic acidHCID 68291372Tert-butyl 10-benzyl-8-vinyl-7-oxa-3,10-diazaspiro[5.5]undecane-3-carboxylate

Produkt 1

HCID 86672478(8-Benzyl-10-vinyl-11-oxa-3,8-diazaspiro[5.5]undecan-3-yl)-(4-isopropoxy-3-methyl-phenyl)methanoneAusbeute 99 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 702EthanolLösungsmittelHCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

To tert-butyl 8-benzyl-10-vinyl-11-oxa-3,8-diazaspiro[5.5]undecane-3-carboxylate (600 mg, 1.61 mmol) in ethanol (1 mL) was added HCl (4.028 mL of 4 M in dioxane, 16.11 mmol) and the reaction mixture was stirred for 30 minutes. The reaction mixture was concentrated in vacuo, then DMF (4 mL), 4-isopropoxy-3-methyl-benzoic acid (313 mg, 1.61 mmol) and HATU (613 mg, 1.61 mmol) were added and the reaction mixture was stirred for 10 minutes. Triethylamine (898 μL, 6.44 mmol) was added and the reaction mixture was stirred for 16 hours, The reaction mixture was concentrated in vacuo, diluted with DCM (5 mL), washed with 1 N aq. NaOH (2 mL) and brine (2 mL), dried over MgSO4, filtered and concentrated in vacuo. The crude material was purified by silica gel column chromatography using 0-100% EtOAc/hexanes eluent to give (8-benzyl-10-vinyl-11-oxa-3,8-diazaspiro[5.5]undecan-3-yl)-(4-isopropoxy-3-methyl-phenyl)methanone (715 mg, 99%) as a pale yellow oil. 1H NMR (400 MHz, CDCl3) δ 7.35-7.22 (m, 5H), 7.20-7.14 (m, 2H), 6.79 (d, J=8.2 Hz, 1H), 5.83-5.74 (m, 1H), 5.34-5.26 (m, 1H), 5.15 (d, J=10.6 Hz, 1H), 4.59-4.50 (m, 1H), 4.33-4.14 (m, 2H), 3.59-3.14 (m, 7H), 2.79 (d, J=11.0 Hz, 1H), 2.56 (d, J=11.1 Hz, 1H), 2.19 (s, 3H), 1.91-1.80 (m, 2H), 1.69-1.39 (m, 2H), 1.34 (d, J=6.0 Hz, 6H); ESI-MS m/z calc. 448.6. Found 449.5 (M+1)+; Retention time: 1.48 minutes (3 min run).

Aufarbeitung

  1. concentrationThe reaction mixture was concentrated in vacuo
  2. stirringthe reaction mixture was stirred for 10 minutes
  3. stirringthe reaction mixture was stirred for 16 hours
  4. concentrationThe reaction mixture was concentrated in vacuo
  5. additiondiluted with DCM (5 mL)
  6. washwashed with 1 N aq. NaOH (2 mL) and brine (2 mL)
  7. dry with materialdried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customThe crude material was purified by silica gel column chromatography

Quellen und Nachweise

ORD-Eintrag
ord-3631e90ce3224ceb96afd77885c9b1df
Quelldatensatz
uspto-grants-2014_09
Patentnummer
US08828996B2

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