Water → benzyl (5S)-N,N-bis(tert-butoxycarbonyl)-5-(2,3-difluorophenyl)-6-nitro-D-norleucinate

HRID 501132

Reaktionsgleichung

Reaktionsgleichung von HRID 501132
[C:1]([O:5][C:6]([N:8]([C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])[C@H:9]([CH2:20][CH2:21]/[CH:22]=[CH:23]/[N+:24]([O-:26])=[O:25])[C:10]([O:12][CH2:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)=[O:11])=[O:7])([CH3:4])([CH3:3])[CH3:2].[F:34][C:35]1[C:40]([F:41])=[CH:39][CH:38]=[CH:37][C:36]=1B(O)O.O.C(=O)(O)[O-].[Na+]>O1CCOCC1.C(Cl)Cl.C([O-])(O)=O.[Na+].C1C=CC(P(C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:1]([O:5][C:6]([N:8]([C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])[C@@H:9]([C:10]([O:12][CH2:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)=[O:11])[CH2:20][CH2:21][C@@H:22]([C:39]1[CH:38]=[CH:37][CH:36]=[C:35]([F:34])[C:40]=1[F:41])[CH2:23][N+:24]([O-:26])=[O:25])=[O:7])([CH3:4])([CH3:3])[CH3:2]

Komponenten

8

Edukt 4

HCID 962WaterHCID 516892Sodium BicarbonateHCID 2734333(2,3-Difluorophenyl)boronic acidHCID 25034374benzyl (2R,5E)-2-[bis(tert-butoxycarbonyl)amino]-6-nitrohex-5-enoate

Produkt 1

HCID 25034375benzyl (5S)-N,N-bis(tert-butoxycarbonyl)-5-(2,3-difluorophenyl)-6-nitro-D-norleucinateAusbeute 87,4 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 634876Binap, (A+-)-Katalysator2×HCID 312751,4-DioxaneLösungsmittelHCID 23716255Sodium bicarbonate methylene chlorideLösungsmittel

Versuchsvorschrift

A solution of benzyl (2R,5E)-2-[bis(tert-butoxycarbonyl)amino]-6-nitrohex-5-enoate (34.0 g, 73.2 mmol), 2,3-difluorophenylboronic acid (28.9 g, 183.0 mmol) and water (4.62 mL, 256.2 mmol) in dioxane (240 mL) was degassed with argon for 15 min. To this solution was added sodium bicarbonate (3.08 g, 36.6 mmol), (S)-BINAP (1.28 g, 2.05 mmol) and acetylacetanotobis(ethylene)rhodium(I) (0.472 g, 1.83 mmol). The mixture was stirred at RT for 2 min then heated to 35° C. After 4 h, 255 mg of (S)-BINAP and 94 mg of acetylacetanotobis(ethylene)rhodium(I) were added. After an additional 2 h the reaction was diluted with DCM/NaHCO3, the layers separated and the aqueous phase was backwashed with another portion of DCM. The combined organics were dried over magnesium sulfate, filtered and concentrated to give a residue that was purified by silica gel chromatography (5%→60% ethyl acetate/hexanes) to give the title compound (37.0 g, 87%) contaminated with ˜5% 5R isomer. MS 379.1 (M+1-2Boc).

Aufarbeitung

  1. temperaturethen heated to 35° C
  2. waitAfter 4 h
  3. customthe layers separated
  4. dry with materialThe combined organics were dried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customto give a residue that
  8. customwas purified by silica gel chromatography (5%→60% ethyl acetate/hexanes)

Quellen und Nachweise

ORD-Eintrag
ord-e4c6aaf95b64446b98c6b23410e8d15e
Quelldatensatz
uspto-grants-2010_08
Patentnummer
US07772224B2

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