Acetic Acid → Methyl(1R,2R,5S,6S)-2-{[tert-butyl(dimethyl)silyl]oxy}-6-fluoro-4-oxobicyclo[3.1.0]hexane-6-carboxylate

HRID 507819Notes

Reaction equation

HRID 507819 reaction equation
[CH3:1][O:2][C:3]([C@:5]1([F:20])[C@@H:10]2[C@H:6]1[C@@H:7]([OH:19])[CH2:8][C@H:9]2[O:11][Si:12]([C:15]([CH3:18])([CH3:17])[CH3:16])([CH3:14])[CH3:13])=[O:4].C(O)(=O)C.O.Cl[O-].[Na+]>C(#N)C.CO.CC(OC)(C)C.CCCCCC.C(O)(C)C>[Si:12]([O:11][C@@H:9]1[CH2:8][C:7](=[O:19])[C@@H:6]2[C@H:10]1[C@@:5]2([F:20])[C:3]([O:2][CH3:1])=[O:4])([C:15]([CH3:18])([CH3:17])[CH3:16])([CH3:14])[CH3:13]

Participants

9

Reactant 4

HCID 176Acetic AcidHCID 962WaterHCID 11681051Methyl(1R,2R,4S,5S,6R)-2-{[tert-butyl(dimethyl)silyl]oxy}-6-fluoro-4-hydroxybicyclo[3.1.0]hexane-6-carboxylate2×HCID 23665760Sodium Hypochlorite2×

Product 1

HCID 11587530Methyl(1R,2R,5S,6S)-2-{[tert-butyl(dimethyl)silyl]oxy}-6-fluoro-4-oxobicyclo[3.1.0]hexane-6-carboxylate

Reagents, catalysts & solvents 4

HCID 887MethanolSolventHCID 3776IsopropanolSolventHCID 6342AcetonitrileSolventHCID 21982663Methyl t-butylether hexaneSolvent

Procedure

To a solution of bicyclic mono-TBS-diol 5 (2.08 kg; 6.83 mol) in acetonitrile (8.0 L) at −5° C. was added acetic acid (0.70 L) and water (2.5 L), followed by RuCl3 hydrate (14.20 g). To the mixture was added aqueous sodium hypochlorite solution (˜13%; 7.0 L) over 2 h, keeping the temperature around 0° C. The resulting mixture was stirred at 0° C. for another 1 h until all bicyclic mono-TBS-diol 5 disappeared, monitoring by TLC and NMR. The excess aqueous sodium hypochlorite was decomposed by the addition of isopropanol (0.70 L), aged at 0° C. for 15 min. The two layers were cut and the aqueous layer was discarded. The solution was used for the next reaction without further treatment. Analytical pure sample was obtained by flash silica gel column chromatography (MTBE/hexane) as colorless crystals: mp 70-71° C.; 1H NMR (400 MHz, CDCl3): δ 4.66 (d, J=5.4 Hz, 1H), 3.86 (s, 3H), 3.73 (s, 3H), 2.73 (m, 2H), 2.54 (dt, J=19.1, 5.7 Hz, 1H), 2.22 (dd, J=19.1, 3.8 Hz, 1H), 0.91 (s, 9H), 0.13 (s, 3H), 0.11 (s, 3H); 13C NMR (101 MHz, CDCl3): δ 206.2, 167.1 (d, J=26.1 Hz), 78.9 (d, J=246.4 Hz), 67.6 (d, J=2.8 Hz), 53.4, 47.5 (d, J=3.9 Hz), 42.0 (d, J=11.4 Hz), 39.6 (d, J=13.3 Hz), 25.7, 18.0, −4.76, and −4.78; 19F NMR (376 MHz, CDCl3): δ −210.7; [α]D25=+58.2 (c 0.50, CH3OH).

Workup

  1. customthe temperature around 0° C
  2. customThe solution was used for the next reaction without further treatment

Sources & evidence

ORD record
ord-4c11e9fd1d0d46199a0439796820885d
Source dataset
uspto-grants-2010_08
Patent number
US07786314B2

Reaction notes

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