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Hydrochloric Acid → (3R,5R,6S)-tert-butyl 3-allyl-2-oxo-5,6-diphenyl-3-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)butyl)morpholine-4-carboxylate

HRID 579478
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Druckvorschau

Reaktionsgleichung

Reaktionsgleichung von HRID 579478
[O:1]=[C:2]1[O:7][C@@H:6]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)[C@@H:5]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[N:4]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[C@@H:3]1[CH2:27][CH2:28][CH2:29][CH2:30][B:31]1[O:35][C:34]([CH3:37])([CH3:36])[C:33]([CH3:39])([CH3:38])[O:32]1.CN(CCN(C)C)C.[CH2:48](I)[CH:49]=[CH2:50].C[Si]([N-][Si](C)(C)C)(C)C.[K+].Cl>C1COCC1.CCCCCCC>[CH2:50]([C@:3]1([CH2:27][CH2:28][CH2:29][CH2:30][B:31]2[O:35][C:34]([CH3:37])([CH3:36])[C:33]([CH3:39])([CH3:38])[O:32]2)[C:2](=[O:1])[O:7][C@@H:6]([C:8]2[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=2)[C@@H:5]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[N:4]1[C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH:49]=[CH2:48]
KomponentenVersuchsvorschriftAufarbeitungQuellen und NachweiseNotizen zur Reaktion

Komponenten

8

Edukt 5

HCID 313Hydrochloric AcidHCID 8037N,N,N',N'-TetramethylethylenediamineHCID 11166Allyl iodideHCID 3251421Potassium bis(trimethylsilyl)amideHCID 66833293tert-Butyl (3R,5R,6S)-2-oxo-5,6-diphenyl-3-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)butyl)morpholine-4-carboxylate

Produkt 1

HCID 66833488
(3R,5R,6S)-tert-butyl 3-allyl-2-oxo-5,6-diphenyl-3-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)butyl)morpholine-4-carboxylate
Ausbeute 96,7 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 8028TetrahydrofuranLösungsmittelHCID 8900HeptaneLösungsmittel

Versuchsvorschrift

A solution of (3R,5R,6S)-tert-butyl 2-oxo-5,6-diphenyl-3-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)butyl)morpholine-4-carboxylate (5.00 g, 9.34 mmol) and TMEDA (10 mL, 65 mmol, 7 equiv) in THF (51 mL, 0.2 M) was cooled to −78° C. and treated with allyl iodide (17 mL, 187 mmol, 20 equiv) and potassium bis(trimethylsilyl)amide (47 mL, 0.9 M in THF, 46.7 mmol, 5 equiv) drop wise and stirred for 30 min. Once the addition was complete, the cooling bath was removed and the mixture was stirred over night. Once complete by TLC, the reaction mixture was quenched with 0.5N HCl (5-10 equiv), diluted with heptane and washed successively with water and saturated aqueous NaCl, dried over MgSO4, filtered and concentrated. Purification by MPLC (1-60% ethyl acetate in heptane over 6 CV) gave (3R,5R,6S)-tert-butyl 3-allyl-2-oxo-5,6-diphenyl-3-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)butyl)morpholine-4-carboxylate as colorless oil (5.2 g, 96%). Rf 0.55 (30% ethyl acetate in heptane); 1H NMR (CDCl3, 300 MHz) δ 7.39-7.14 (m, 10H), 7.10 (dd, J1=5.4 Hz, J2=1.8 Hz, 1H), 6.08 (d, J=5.4 Hz, 1H), 5.95-5.80 (m, 1H), 5.27-5.17 (m, 2H), 3.30-3.15 (m, 1H), 2.89-2.76 (m, 1H), 2.20-2.07 (m, 2H), 1.54 (s, 9H), 1.35-1.21 (m, 4H), 1.78 (s, 12H), 0.46 (t, J=8.4 Hz, 2H); ESI-LCMS m/z calcd for C34H46BNO6: expected 575.3. found 574.3 (M+H)+.

Aufarbeitung

  1. additionOnce the addition
  2. customthe cooling bath was removed
  3. stirringthe mixture was stirred over night
  4. washwashed successively with water and saturated aqueous NaCl
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customPurification by MPLC (1-60% ethyl acetate in heptane over 6 CV)

Quellen und Nachweise

ORD-Eintrag
ord-20be37497fa24a609bdcf9720a56a7db
Quelldatensatz
uspto-grants-2015_05
DOI
10.6084/m9.figshare.5104873.v1
Patentnummer
US09040703B2

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