Imidazole → 9-Benzyloxy-4,4,6,8-tetramethyl-5-oxo-7-(2,2,2-trichloroethoxycarbonyloxy)-3-(triethylsilanyloxy)-nonanoic Acid Tert-Butyl Ester

HRID 254456Notes

Reaction equation

HRID 254456 reaction equation
[C:1]([O:5][C:6](=[O:38])[CH2:7][CH:8]([OH:37])[C:9]([CH3:36])([CH3:35])[C:10](=[O:34])[CH:11]([CH3:33])[CH:12]([O:24][C:25]([O:27][CH2:28][C:29]([Cl:32])([Cl:31])[Cl:30])=[O:26])[CH:13]([CH3:23])[CH2:14][O:15][CH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)([CH3:4])([CH3:3])[CH3:2].N1C=CN=C1.[Si:44](Cl)([CH2:49][CH3:50])([CH2:47][CH3:48])[CH2:45][CH3:46]>CN(C=O)C.C([O-])(O)=O.[Na+]>[C:1]([O:5][C:6](=[O:38])[CH2:7][CH:8]([O:37][Si:44]([CH2:49][CH3:50])([CH2:47][CH3:48])[CH2:45][CH3:46])[C:9]([CH3:36])([CH3:35])[C:10](=[O:34])[CH:11]([CH3:33])[CH:12]([O:24][C:25]([O:27][CH2:28][C:29]([Cl:30])([Cl:32])[Cl:31])=[O:26])[CH:13]([CH3:23])[CH2:14][O:15][CH2:16][C:17]1[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=1)([CH3:3])([CH3:2])[CH3:4]

Participants

6

Reactant 3

HCID 795ImidazoleHCID 13819ChlorotriethylsilaneHCID 208175859-Benzyloxy-3-hydroxy-4,4,6,8-tetramethyl-5-oxo-7-(2,2,2-trichloroethoxycarbonyloxy)-nonanoic Acid Tert-Butyl Ester

Product 1

HCID 668509949-Benzyloxy-4,4,6,8-tetramethyl-5-oxo-7-(2,2,2-trichloroethoxycarbonyloxy)-3-(triethylsilanyloxy)-nonanoic Acid Tert-Butyl EsterYield 510.4%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 516892Sodium BicarbonateSolvent

Procedure

To a solution of 70 (37.6 mg, 6.3 μmol) and imidazole (9.4 mg, 13.8 μmol) in DMF (0.4 mL) at 0° C. was added TESCl (11.6 μL, 69.3 μmol). After 3 h, the mixture was diluted with sat aq NaHCO3. The aqueous layer was extracted three times with hexanes. The combined organic extracts were washed with brine, dried over MgSO4 and concentrated under reduced pressure. The crude product was purified by flash chromatography (gradient hexane to hexane/EtOAc 93:7) to yield, in order of elution, 71 (22.9 mg, 51%), and recovered 70 (12.9 mg, 34%) as clear oils. 7: 1H NMR (400 MHz, CDCl3) δ 0.66 (q, J=7.9 Hz, 6H), 0.96 (t, J=7.9 Hz, 9H), 1.01 (s, 3H), 1.05 (d, J=5.2 Hz, 3H), 1.07 (d, J=5.3 Hz, 3H), 1.35 (s, 3H). 1.44 (s, 9H), 2.05-2.11 (m, 2H), 2.50 (dd, J=3.5 and 17.2 Hz, 1H), 3.35 (dd, J=5.9 and 9.0 Hz, 1H), 3.49 (dd, J=4.0 and 9.0 Hz, 1H), 3.53 (dd, J=3.8 and 6.7 Hz, 1H), 4.18 (dd, J=3.5 and 6.5 Hz, 1H), 4.45 (s, 2H), 4.65 (d, J=11.9 Hz, 1H), 4.79 (d, J=11.9 Hz, 1H), 4.97 (dd, J=3.7 and 8.1 Hz, 1H), 7.29-7.52 (m, 5H); 13C NMR (125 MHz, CDCl3) δ 5.3, 7.3, 10.9, 14.9, 21.3, 22.6, 28.4, 35.9, 41.1, 42.7, 53.7, 71.9, 73.7, 75.7, 80.1, 80.9, 95.1, 127.9, 128.0, 128.7, 138.6, 154.3, 171.7, 215.7; IR (film, NaCl, cm−1) 2956, 2876, 1732, 1694, 1456, 1366, 1257, 1154, 1098, 988, 835, 774, 741; LRMS (ESI) calcd for C33H53O8SiCl3Na [M+Na+] 733.2, found 733.3. [α]23D=−16.1 (c=0.1, CHCl3).

Workup

  1. extractionThe aqueous layer was extracted three times with hexanes
  2. washThe combined organic extracts were washed with brine
  3. dry with materialdried over MgSO4
  4. concentrationconcentrated under reduced pressure
  5. customThe crude product was purified by flash chromatography (gradient hexane to hexane/EtOAc 93:7)

Sources & evidence

ORD record
ord-fde11bdba3e04bc3a37841f9f05fd8b1
Source dataset
uspto-grants-2011_01
Patent number
US07875638B2

Reaction notes

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