| 77% |
With potassium osmate(VI) dihydrate; sodium periodate In tetrahydrofuran; water at 15 - 20℃; for 4h; |
1.8.2 1.8.2 Preparation of Compound 4
To a solution of compound 3 (212 mg, 1 mmol) in THF/H2O (3 mL/3 mL) were added K2OsO4.2H2O (18 mg, 0.05 mmol) and NaIO4 (491 mg, 2.3 mmol) at room temperature, then the mixture was stirred at 15° C. for 4 h. TLC showed starting material was consumed completely. The mixture was concentrated in vacuo. The residue was purified by silica gel column (PE:EA=5:1) to give compound 4 as yellow oil (170 mg, 77%). LCMS: 216 [M+1]. |
| 77% |
With potassium osmate(VI) dihydrate; sodium periodate In tetrahydrofuran; water at 15℃; for 4h; |
I.1.8.2 1.8.2 Preparation of Compound 4
To a solution of compound 3 (212 mg, 1 mmol) in THF/H2O (3 mL/3 mL) were added K2OsO4.2H2O (18 mg, 0.05 mmol) and NaIO4 (491 mg, 2.3 mmol) at room temperature, then the mixture was stirred at 15° C. for 4 h. TLC showed starting material was consumed completely. The mixture was concentrated in vacuo. The residue was purified by silica gel column (PE:EA=5:1) to give compound 4 as yellow oil (170 mg, 77%). LCMS: 216 [M+1]. |
| 61% |
Stage #1: tert-butyl 6-methylidene-1,4-oxazepan-4-carboxylate With osmium(VIII) oxide In tetrahydrofuran; water; <i>tert</i>-butyl alcohol at 25℃; for 0.5h;
Stage #2: With sodium periodate In tetrahydrofuran; water; <i>tert</i>-butyl alcohol at 25℃; for 16h; |
15.1 Step 1:
To a mixture of tert-butyl 6-m ethylene- l,4-oxazepane-4-carboxylate (1.30 g, 6.10 mmol) in THF (13 mL) and H2O (13 mL) was added 0s04 [11.92 mg, 0.047 mmol, 2.5% wt in /-BuOH (prepared by 0.25 g 0s04 dissolved in 9.75 g /-BuOH)]. The mixture was stirred at 25 °C for 0.5 h then NaI04 (3.91 g, 18.29 mmol) was added and the mixture was stirred at 25 °C for 16 h. The mixture was diluted with H2O (50 mL) and extracted with EA (20 mL x 3). The combined organic layers were washed with brine, dried over Na2SC>4, filtered and concentrated. The residue was purified by column chromatography and the eluent was concentrated to afford compound 24 (830 mg, 61%) as a colorless oil. LCMS (ESI, m/z): 160.2 [M-56]+. |
|
With sodium periodate; osmium(VIII) oxide In 1,4-dioxane; water; <i>tert</i>-butyl alcohol at 20℃; for 48h; |
45 Preparation 45: 6-OXO- [1, 4] OXAZEPANE-4-CARBOXYLIC acid tert-butyl ester
Sodium periodate (1.0 g, 4.69 MMOL), followed by osmium tetroxide (0.15 ML, 2.5wt% solution in tert-butanol, 0.014 MMOL), were added to a suspension of the alkene from preparation 44 (500 mg, 2.34 MMOL) in dioxan (10 mi) and water (10 ml) and the reaction stirred at room temperature for 48 hours. The reaction was diluted with water (50 ML), brine added, and the mixture extracted with ethyl acetate. The combined organic extracts were dried over magnesium sulphate and evaporated under reduced pressure to afford the title compound as a brown oil, 567 mg. H NMR (400MHZ, CDCl3) : 8 1.47 (s, 9H), 3.68 (m, 2H), 3.91 (br m, 2H), 4.06 (br m, 2H), 4.11 (s, 2H). APCI m/z 233 [M+NH4] + |
|
With sodium periodate; osmium(VIII) oxide In 1,4-dioxane; water; <i>tert</i>-butyl alcohol at 20℃; for 18h; |
38
A solution of tert- butyl 6-methylene- l ,4-oxazepane-4-carboxylate 38.2 (1.23 g, 5.74 mmol) in 1 ,4-dioxane (20 mL) and H20 (20 mL) was treated with sodium periodate (2.46 g, 1 1.49 mmol) and a solution of 2.5% Os04 in i-BuOH (0.36 mL, 0.028 mmol). The reaction mixture was stirred at room temperature for 18 hrs. The resulting yellow-white suspension was diluted with H20 and extracted with EtOAc (2x50 mL). The combined organic layers were dried over MgSC>4, filtered, and concentrated in vacuo to provide a brown oil (1.30 g) that was used immediately without further purification. |
|
With sodium periodate; osmium(VIII) oxide In 1,4-dioxane; water; <i>tert</i>-butyl alcohol at 20℃; for 48h; |
10.2 Step 2: preparation of tert-butyl 6-oxo-1 ,4-oxazepane-4-carboxylate
Step 2: preparation of tert-butyl 6-oxo-1 ,4-oxazepane-4-carboxylate. To a solution of tert-butyl 6-methylene-1 , 4-oxazepane-4-carboxylate (4.0 g, 18.76 m mol) indioxane (80 mL) was added a solution of sodium periodate (8.0 g, 37.4 mmol) in water (80 mL), followed by 1.2 mL of a 2.5% wt solution of osmium tetroxide in tert-butanol. The reaction was allowed to stir at ambient temperature for 48h, after which water and brine were added, and the desired product was extracted into ethyl acetate. The combined organic layers were dried over magnesium sulfate and concentrated in vacuo.The resulting brown oil was passed through a silica gel plug to afford the title compound as a clear oil. |
| 1.7 g |
With sodium periodate; osmium(VIII) oxide In tetrahydrofuran; water at 20℃; for 4h; |
T-55 Example T-55: Oxidation olefin to ketone
To a solution of tert-butyl 6-methylene-1,4-oxazepane-4-carboxylate (1.8 g, 8.44 mmol) in THF (30 mL) and H2O (30 mL) was added sodium periodate (3.61 g, 16.88 mmol) and osmium(VIII) oxide (0.11 g, 0.42 mmol). The reaction was stirred at ambient temperature for 4 h. Water (20 mL) was added to the reaction vessel and the resulting biphasic mixture was extracted with DCM (3 x 100 mL). The organic phase was washed with saturated aqueous NaCl (1 x 20 mL). The combined organics were dried over anhydrous Na2SO4, filtered and concentrated in vacuo. The resulting oil was purified by flash column chromatography with a gradient elution of hexanes (100%) to hexanes (40%) and EtOAc (60%) to provide tert-butyl 6-oxo-1,4-oxazepane-4-carboxylate (1.7 g, 7.9 mmol) as a colorless oil. |
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