Carbonic Acid → HCID 11558955, compound

HRID 491340Notes

Reaction equation

HRID 491340 reaction equation
[Si:1]([O:8][C@H:9]1[C:14](=CCCOCOC)[C@H:13]([O:22][Si](C(C)(C)C)(C)C)[CH2:12][C:11](=[O:30])[CH2:10]1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].O[C:32]([OH:34])=O.N1C(C)=CC=C[C:36]=1[CH3:42].[O:43]([Si](C(C)(C)C)(C)C)S(C(F)(F)F)(=O)=O.[OH2:58]>C(Cl)Cl.C1C=CC=CC=1>[C:36]([O:30][C@@:11]12[CH2:12][C@@H:13]([O:22][C:32]1=[O:34])[C:14](=[O:43])[C@H:9]([O:8][Si:1]([C:4]([CH3:5])([CH3:6])[CH3:7])([CH3:3])[CH3:2])[CH2:10]2)(=[O:58])[CH3:42]

Participants

8

Reactant 5

HCID 767Carbonic AcidHCID 962Water2×HCID 79372,6-LutidineHCID 123564tert-Butyldimethylsilyl trifluoromethanesulphonateHCID 11510886HCID 11510886, compound

Product 1

HCID 11558955HCID 11558955, compound

Reagents, catalysts & solvents 2

HCID 241BenzeneSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
-50 °C

Procedure

[(3R,5R)-3,5-Bis[(tert-Butyldimethylsilyl)oxy]-4-[3′-(methoxymethoxy)propylidene]cyclohexanone (11). To a solution of hydroxy ketone 9 (40 mg, 117 μmol) in anhydrous CH2Cl2 (0.4 mL) at −50° C. was added 2,6-lutidine (32 μL, 274 μmol) and t-butyldimethylsilyl triflate (56 μL, 240 μmol). The mixture was stirred for 5 min at −50° C., then it was allowed to warm up to −15° C. and stirred at this temperature for additional 30 min. Benzene and water was added and the mixture was poured into water and extracted with benzene. The extract was washed with saturated CuSO4 and water, dried (MgSO4), and evaporated. The oily residue was redissolved in hexane, and purified by flash chromatography on silica. Elution with hexane/ethyl acetate (95:5) gave pure protected ketone 11 as a colorless oil (30 mg, 57%; 66% based on recovered substrate) and unreacted 9 (6 mg). 11: [α]24D−26° (c 0.30 CHCl3); 1H NMR (400 MHz, CDCl3) δ 0.019 and 0.065 (3H and 9H, each s, 4×SiCH3), 0.838 and 0.912 (9H and 9H, each s, 2×Si-t-Bu), 2.32 (1H, dd, J=14.1, 10.4 Hz, 2α-H), 2.45 (3H, br m, ═C—CH2 and 6α-H), 2.53 (1H, ddd, J=14.4, 3.2, 2.1 Hz, 6β-H), 2.75 (1H, ddd, J=14.1, 5.6, 2.1 Hz, 2β-H), 3.36 (3H, s, O—CH3), 3.58 (2H, m, CH2—CH2—O), 4.62 (2H, s, O—CH2—O), 4.75 (1H, ddd, J=10.4, 5.6, 1.4 Hz, 3β-H), 5.01 (1H, t, J˜3.2 Hz, 5α-H), 5.70 (1H, dt, J=1.7, 7.8 Hz, ═CH); 13C NMR (125 MHz) δ −5.08 (Si—CH3), −5.06 (Si—CH3), −5.05 (Si—CH3), −5.00 (Si—CH3), 17.9 [C(CH3)3], 25.5 [C(CH3)3], 27.7 (CH2—CH2—C═), 50.2 (C6), 52.4 (C2), 55.2 (O—CH3), 65.8 (C3), 67.1 (O—CH2—CH2), 67.8 (C5), 96.4 (O—CH2—O), 118.5 (═C—CH2), 141.5 (C4), 207.5 (C1); MS (EI) m/z (relative intensity) 443 (M++H, 2), 427 (M+−CH3, 5), 401 (55), 371 (15), 339 (20), 75 (100); exact mass calcd for C12H43O4Si2 (M+−CH3) 427.2700, measured 427.2701.

Workup

  1. temperatureto warm up to −15° C.
  2. stirringstirred at this temperature for additional 30 min
  3. extractionextracted with benzene
  4. washThe extract was washed with saturated CuSO4 and water
  5. dry with materialdried (MgSO4)
  6. customevaporated
  7. dissolutionThe oily residue was redissolved in hexane
  8. custompurified by flash chromatography on silica
  9. washElution with hexane/ethyl acetate (95:5)
  10. customgave pure
  11. customketone 11 as a colorless oil (30 mg, 57%; 66% based on recovered substrate) and unreacted 9 (6 mg)

Sources & evidence

ORD record
ord-457a208969df4729bc08f29c85bae53d
Source dataset
uspto-grants-2009_05
Patent number
US07531527B2

Reaction notes

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