Diethyl methylphosphonate → diethyl (((2S,3S,4R,5R,6S)-3,4,5-tris(benzyloxy)-2-hydroxy-6-methyltetrahydro-2H-pyran-2-yl)methyl)phosphonate

HRID 522166Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 522166
C([Li])CCC.[CH3:6][P:7](=[O:14])([O:11][CH2:12][CH3:13])[O:8][CH2:9][CH3:10].[CH2:15]([O:22][C@H:23]1[C@H:28]([O:29][CH2:30][C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=2)[C@H:27]([O:37][CH2:38][C:39]2[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=2)[C@H:26]([CH3:45])[O:25][C:24]1=[O:46])[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1>C1COCC1>[CH2:15]([O:22][C@H:23]1[C@H:28]([O:29][CH2:30][C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=2)[C@H:27]([O:37][CH2:38][C:39]2[CH:40]=[CH:41][CH:42]=[CH:43][CH:44]=2)[C@H:26]([CH3:45])[O:25][C@@:24]1([CH2:6][P:7](=[O:14])([O:11][CH2:12][CH3:13])[O:8][CH2:9][CH3:10])[OH:46])[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1

Komponenten

5

Edukt 3

HCID 12685Diethyl methylphosphonateHCID 10432954(3S,4R,5R,6S)-3,4,5-tris(benzyloxy)-6-methyltetrahydro-2H-pyran-2-oneHCID 178418339Butyllithium

Produkt 1

HCID 11786599diethyl (((2S,3S,4R,5R,6S)-3,4,5-tris(benzyloxy)-2-hydroxy-6-methyltetrahydro-2H-pyran-2-yl)methyl)phosphonateAusbeute 67,5 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel2×

Versuchsvorschrift

n-Butyllithium (2.5 M in hexanes, 0.64 mL, 1.59 mmol, commercially available from Sigma Aldrich) was added to a stirred solution of diethyl methylphosphonate (0.23 mL, 1.59 mmol, commercially available from Sigma Aldrich) in THF (1.5 mL) at −78° C. under an argon atmosphere. The mixture was stirred for 15 min before a solution of (3 S,4R,5R,6S)-3,4,5-tris(benzyloxy)-6-methyltetrahydro-2H-pyran-2-one (0.275 g, 0.636 mmol) in THF (1 mL) at −78° C. was added. The reaction mixture was removed from the cooling bath, and the mixture was allowed to warm to room temperature while stirring for 1 h. The reaction mixture was next concentrated in vacuo. The resulting oil was purified by silica gel chromatography (0 to 75% EtOAc/hexanes gradient) to give diethyl (((2S,3S,4R,5R,6S)-3,4,5-tris(benzyloxy)-2-hydroxy-6-methyltetrahydro-2H-pyran-2-yl)methyl)phosphonate as a colorless oil (0.251 g, 67.5% yield). 1H NMR (400 MHz, CDCl3): δ ppm 1.09 (d, J=6.65 Hz, 3 H) 1.26 (q, J=6.85 Hz, 6 H) 1.76 (dd, J=18.49, 15.16 Hz, 1 H) 2.33 (dd, J=17.41, 15.26 Hz, 1 H) 3.68 (br. d, J=1.60 Hz, 1 H) 3.72 (d, J=9.98 Hz, 1 H) 3.92-4.02 (m, 2 H) 4.06-4.17 (m, 4 H) 4.69 (dd, J=11.54, 4.11 Hz, 2H) 4.77 (dd, J=16.43, 11.74 Hz, 2 H) 4.99 (dd, J=11.54, 9.39 Hz, 2 H) 7.26-7.41 (m, 15 H).

Aufarbeitung

  1. customat −78° C.
  2. additionwas added
  3. customThe reaction mixture was removed from the cooling bath
  4. concentrationThe reaction mixture was next concentrated in vacuo
  5. customThe resulting oil was purified by silica gel chromatography (0 to 75% EtOAc/hexanes gradient)

Quellen und Nachweise

ORD-Eintrag
ord-ac20e89193fc476f83020c36cbf7c257
Quelldatensatz
uspto-grants-2016_05
Patentnummer
US09328134B2

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