Reaktion #2000633

Reaktionsgleichung

tert-butyl 2,7-diazaspiro[3.5]nonane-7-carboxylate

5-bromoindanone

Sodium triacetoxyborohydride

→

desired product

Ausbeute 76.0%

tert-Butyl 2-(-(1R)-5-bromo-2,3-dihydro-1H-inden-1-yl)-2,7-diazaspiro[3.5]nonane-7-carboxylate

Ausbeute 76.0%

Lösungsmittel

dichloroethane

Reaktionsbedingungen

Aufarbeitung

1. 1
   SonstigeIn a dry 1 L flask was combined
2. 2
   workup.STIRRINGthe reaction was stirred at room temperature for an additional 16 hours
3. 3
   SonstigeThe reaction was quenched with 400 mL saturated sodium bicarbonate
4. 4
   workup.STIRRINGwas stirred for 15 minutes
5. 5
   Sonstigeresulting in a clear bi-phasic mixture
6. 6
   SonstigeThe two layers were separated
7. 7
   Extraktionthe aqueous layer was extracted twice with dichloromethane
8. 8
   WaschenThe combined organic layers were washed with brine
9. 9
   Trocknendried over anhydrous sodium sulfate
10. 10
    Filtrationfiltered
11. 11
    Einengenconcentrated
12. 12
    Sonstigeto afford 17 g of a crude product as a brown oil
13. 13
    SonstigeThis material was purified via Analogix (Analogix Inc., Burlington, Wis.) chromatography
14. 14
    Wascheneluting with 100:0→85:15 dichloromethane/methanol over 30 minutes

Vorschrift

In a dry 1 L flask was combined tert-butyl 2,7-diazaspiro[3.5]nonane-7-carboxylate (6.53 g, 30.9 mmol) and 5-bromoindanone (7.00 g, 30.9 mmol) in 200 mL dichloroethane. Titanium (IV) isopropoxide (18.3 mL, 61.8 mmol) was added and the reaction was stirred at room temperature for 2 hours. Sodium triacetoxyborohydride (26.2 g, 123.6 mmol) was added and the reaction was stirred at room temperature for an additional 16 hours. The reaction was quenched with 400 mL saturated sodium bicarbonate and was stirred for 15 minutes. The mixture was passed through a thin layer of Celite®, resulting in a clear bi-phasic mixture. The two layers were separated and the aqueous layer was extracted twice with dichloromethane. The combined organic layers were washed with brine, dried over anhydrous sodium sulfate, filtered and concentrated to afford 17 g of a crude product as a brown oil. This material was purified via Analogix (Analogix Inc., Burlington, Wis.) chromatography eluting with 100:0→85:15 dichloromethane/methanol over 30 minutes to afford the desired product (9.82 g, 76%) as a brown foam. The enantiomers were separated via preparative chiral HPLC (Column chiralcel OJ-H, 250 mm×4.6 mm, flow-rate 2.5 ml/min, CO2/MeOH (80/20/) mobile phase with 0.1% isopropylamine) to afford the desired product (3-1a, 4.6 g, 36%). MS (ES+) 422.3 (M+H)+. 1H NMR (CDCl3) δ 1.44 (s, 9H), 1.67 (dd, 4H), 1.84-1.93 (m, 1H), 2.07-2.16 (m, 1H), 2.72-2.81 (m, 1H), 2.95-3.15 (m, 5H), 3.31 (dd, 4H), 3.85 (br s, 1H), 7.12 (d, 1H), 7.28 (br s, 1H), 7.35 (br s, 1H).

Quelle