1,1-Dimethylethyl (2S,3R)-6-oxo-2,3-diphenyl-4-morpholinecarboxylate → tert-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

HRID 579477Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 579477
[O:1]=[C:2]1[CH2:7][N:6]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[C@H:5]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[C@H:4]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[O:3]1.I[CH2:28][CH2:29][CH2:30][CH2:31][B:32]1[O:36][C:35]([CH3:38])([CH3:37])[C:34]([CH3:40])([CH3:39])[O:33]1.C[Si]([N-][Si](C)(C)C)(C)C.[Na+]>C1COCC1.CN(P(N(C)C)(N(C)C)=O)C>[O:1]=[C:2]1[O:3][C@@H:4]([C:21]2[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=2)[C@@H:5]([C:15]2[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=2)[N:6]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[C@@H:7]1[CH2:28][CH2:29][CH2:30][CH2:31][B:32]1[O:36][C:35]([CH3:38])([CH3:37])[C:34]([CH3:39])([CH3:40])[O:33]1

Komponenten

6

Edukt 3

HCID 9812251,1-Dimethylethyl (2S,3R)-6-oxo-2,3-diphenyl-4-morpholinecarboxylateHCID 2724254Sodium bis(trimethylsilyl)amideHCID 668332412-(4-Iodobutyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane

Produkt 1

HCID 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-carboxylateAusbeute 94 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 8028TetrahydrofuranLösungsmittelHCID 12679HexamethylphosphoramideLösungsmittel

Versuchsvorschrift

A solution of (2S,3R)-tert-butyl 6-oxo-2,3-diphenylmorpholine-4-carboxylate (4.69 g, 13.27 mmol) and 2-(4-iodobutyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (d 1.38, 5.96 mL, 8.23 g, 26.5 mmol, 2 equiv) in THF (66 mL, 0.2 M) and HMPA (6.6 mL) was cooled to −78° C. and treated with sodium bis(trimethylsilyl)amide (14.6 mL, 1.0 M, 1.1 equiv) drop wise over 5 min and stirred for 1 h. After warming to room temperature and stirring for an additional 2 h, the solution was cooled to 0° C. and quenched with 0.5 NHC (2-3 equiv). The resulting solution was 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 2-oxo-5,6-diphenyl-3-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)butyl)morpholine-4-carboxylate as a white solid (6.66 g, 94%); ESI-LCMS m/z calcd for C31H42BNO2: expected 535.3. found 536.4 (M+H)+.

Aufarbeitung

  1. stirringstirring for an additional 2 h
  2. temperaturethe solution was cooled to 0° C.
  3. customquenched with 0.5 NHC (2-3 equiv)
  4. additionThe resulting solution was diluted with heptane
  5. washwashed successively with water and saturated aqueous NaCl
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customPurification by MPLC (1-60% ethyl acetate in heptane over 6 CV)

Quellen und Nachweise

ORD-Eintrag
ord-9aa567abac124612a8f014bc75734f4d
Quelldatensatz
uspto-grants-2015_05
Patentnummer
US09040703B2

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