Diisopropylamine → 3-Methoxycarbonyl-hexanedioic acid 1-tert-butyl ester

To a solution of n-BuLi (2.5M, 2.6 mL, 71.5 mmol) in anhydrous THF (200 mL) was added anhydrous diisopropyl amine (9.6 mL, 68.30 mmol) at −78° C. After 20 minutes of stirring, a solution of monomethyl glutarate (5 g, 32.5 mmol) in anhydrous THF (20 mL) was added drop wise under controlled temperature. After 30 minutes, a solution of tert-butyl bromoacetate (4.9 mL, 32.50 mmol) in anhydrous THF (20 mL) was slowly added followed by the addition of HMPA (8 mL). The reaction mixture was stirred at −78° C. for an additional 2 h followed by 24 h at room temperature. The reaction mixture was partitioned between HCl (2N, excess) and ethyl acetate. The organic phase was separated and the aqueous phase was extracted several times with ethyl acetate. The recombined organic layer was extracted with brine, dried over sodium sulfate, filtered, and evaporated. The residue was first flashed with chloroform and then with 2–5% methanol in chloroform. The product was obtained as a light yellow oil. 1H-NMR(CDCl3, 400 MH: 1.42(s, 9H); 1.89(m, 2H); 2.24(m, 2H); 2.64(m, 2H); 2.84(m, 1H); 3.69(s, 3H).

1. waitAfter 30 minutes
2. stirringThe reaction mixture was stirred at −78° C. for an additional 2 h
3. waitfollowed by 24 h at room temperature
4. customThe reaction mixture was partitioned between HCl (2N, excess) and ethyl acetate
5. customThe organic phase was separated
6. extractionthe aqueous phase was extracted several times with ethyl acetate
7. extractionThe recombined organic layer was extracted with brine
8. dry with materialdried over sodium sulfate
9. filtrationfiltered
10. customevaporated
11. customThe product was obtained as a light yellow oil

ORD record

ord-c275e65d8caf4126934ce28dca7b57d6

Source dataset

uspto-grants-2006_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07105539B2