Water → 2-acetamido-N-tert-butyl-2-(1-(6-chlorobenzo[d]oxazol-2-yl)piperidin-4-yl)-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)hexanamide

HRID 579560

Reaktionsgleichung

Reaktionsgleichung von HRID 579560
[C:1]([NH:4][C:5]([CH:17]1[CH2:22][CH2:21][N:20]([C:23]2[O:24][C:25]3[CH:31]=[C:30]([Cl:32])[CH:29]=[CH:28][C:26]=3[N:27]=2)[CH2:19][CH2:18]1)([CH2:13][CH2:14][CH:15]=[CH2:16])[C:6]([NH:8][C:9]([CH3:12])([CH3:11])[CH3:10])=[O:7])(=[O:3])[CH3:2].[CH3:33][C:34]1([CH3:41])[C:38]([CH3:40])([CH3:39])[O:37][BH:36][O:35]1.O>ClCCl.[Ir+].ClC1CCC=CCCC=1.C1(P(C2C=CC=CC=2)CCP(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[C:1]([NH:4][C:5]([CH:17]1[CH2:18][CH2:19][N:20]([C:23]2[O:24][C:25]3[CH:31]=[C:30]([Cl:32])[CH:29]=[CH:28][C:26]=3[N:27]=2)[CH2:21][CH2:22]1)([CH2:13][CH2:14][CH2:15][CH2:16][B:36]1[O:37][C:38]([CH3:40])([CH3:39])[C:34]([CH3:41])([CH3:33])[O:35]1)[C:6]([NH:8][C:9]([CH3:12])([CH3:11])[CH3:10])=[O:7])(=[O:3])[CH3:2]

Komponenten

7

Edukt 3

HCID 962WaterHCID 27347684,4,5,5-Tetramethyl[1,3,2]dioxaborolaneHCID 668329552-acetamido-N-tert-butyl-2-(1-(6-chlorobenzo[d]oxazol-2-yl)piperidin-4-yl)hex-5-enamide

Produkt 1

HCID 668329422-acetamido-N-tert-butyl-2-(1-(6-chlorobenzo[d]oxazol-2-yl)piperidin-4-yl)-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)hexanamideAusbeute 69,2 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 742671,2-Bis(diphenylphosphino)ethaneKatalysatorHCID 178478077HCID 178478077, VerbindungKatalysatorHCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

A solution of 2-acetamido-N-tert-butyl-2-(1-(6-chlorobenzo[d]oxazol-2-yl)piperidin-4-yl)hex-5-enamide (240 mg, 0.52 mmol) in dichloromethane (4 mL), was treated with chloro-1,5-cyclooctadiene iridium(I) dimer (10.4 mg, 3 mol %) and 1,2-bis(diphenylphosphino) ethane (12.2 mg, 6 mol %). The solution was stirred at room temperature for 30 minutes and then 4,4,5,5-tetramethyl-[1,3,2]dioxaborolane (0.152 mL, 1.04 mmol) was added dropwise, and the reaction was stirred overnight at room temperature. The next day, the reaction mixture was poured into water and extracted with ethyl acetate (3×). The combined organic phase was washed with saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate, filtered and concentrated in vacuo. Purification of the crude product by flash column chromatography (silica gel, 30-100% ethyl acetate in heptane) gave 2-acetamido-N-tert-butyl-2-(1-(6-chlorobenzo[d]oxazol-2-yl)piperidin-4-yl)-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)hexanamide as a colorless oil (212 mg, 69%). 1H NMR (CDCl3, 300 MHz) δ 7.24 (d, J=2 Hz, 1H), 7.20 (d, J=8.5 Hz, 1H), 7.12 (dd, J1=8.5 Hz, J2=2 Hz, 1H), 6.97 (s, NH, 1H), 5.48 (s, NH, 1H), 4.32 (m, 2H), 3.02 (m, 2H), 2.84 (m, 1H), 2.47 (tt, J1=12.5 Hz, J2=3 Hz, 1H), 2.01 (s, 3H), 1.86 (m, 2H), 1.30-1.55 (m, 6H), 1.34 (s, 9H), 1.24 (s, 12H), 1.02-1.22 (m, 1H), 0.75 (t, J=7.5 Hz, 2H).

Aufarbeitung

  1. stirringthe reaction was stirred overnight at room temperature
  2. extractionextracted with ethyl acetate (3×)
  3. washThe combined organic phase was washed with saturated aqueous sodium chloride
  4. dry with materialdried over anhydrous magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customPurification of the crude product by flash column chromatography (silica gel, 30-100% ethyl acetate in heptane)

Quellen und Nachweise

ORD-Eintrag
ord-61576a5c05c04658ae5d7b47801f69d2
Quelldatensatz
uspto-grants-2015_05
Patentnummer
US09040703B2

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