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

HRID 20134

Reaction equation

HRID 20134 reaction equation
[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]

Participants

8

Reactant 4

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

Product 1

HCID 25034375benzyl (5S)-N,N-bis(tert-butoxycarbonyl)-5-(2,3-difluorophenyl)-6-nitro-D-norleucinateYield 87.4%

Reagents, catalysts & solvents 3

HCID 634876Binap, (A+-)-Catalyst2×HCID 312751,4-DioxaneSolventHCID 23716255Sodium bicarbonate methylene chlorideSolvent

Procedure

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% SR isomer. MS 379.1 (M+1-2Boc).

Workup

  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)

Sources & evidence

ORD record
ord-385d51baf7bb4af0952a342cb6461589
Source dataset
uspto-grants-2010_06
Patent number
US07745427B2

Linked notes

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