Réaction #1759901

Équation de réaction

2-bromomethyl-1,3-dichloro-5-methoxy-benzene

1-(1,4-Dioxa-spiro[4.5]dec-8-yl)-pyrrolidin-2-one

LDA

→

product

3-(2,6-Dichloro-4-methoxy-benzyl)-1-(1,4-dioxa-spiro[4.5]dec-8-yl)-pyrrolidin-2-one

Solvants

tetrahydrofuran

tetrahydrofuran

Conditions de réaction

Traitement

1. 1
   Autrepurge
2. 2
   Autredid not reach above −67° C
3. 3
   Autreremove the cold bath
4. 4
   Autrereaction
5. 5
   Températureto warm over 3 hr
6. 6
   AutreQuench
7. 7
   Autrethe reaction with saturated aqueous ammonium chloride (100 mL)
8. 8
   Extractionextract with ethyl acetate (3×100 mL)
9. 9
   Séchagedry over anhydrous sodium sulfate
10. 10
    AutrePurify on silica column
11. 11
    Lavageeluting with 8:2 hexanes

Mode opératoire

Cool a solution of 1-(1,4-Dioxa-spiro[4.5]dec-8-yl)-pyrrolidin-2-one (5 g, 22.2 mmol) in tetrahydrofuran (100 mL) to −78° C. under nitrogen purge. Add LDA (2.0 M, 15 mL, 30 mmol) at a rate such that the internal reaction temperature did not reach above −67° C. Stir 30 min at −78° C., add a solution of 2-bromomethyl-1,3-dichloro-5-methoxy-benzene, 6.6 g, 24.4 mmol) in tetrahydrofuran (20 mL) over a 1-2 minute period, remove the cold bath and allow reaction to warm over 3 hr. Quench the reaction with saturated aqueous ammonium chloride (100 mL), extract with ethyl acetate (3×100 mL), combine the extracts and dry over anhydrous sodium sulfate. Purify on silica column eluting with 8:2 hexanes:ethyl acetate to 1:1 hexanes:ethyl acetate to afford the product as a ivory solid, 6.5 g, 71%. 1H NMR (CDCl3) δ 6.86 (s, 2H), 4.06-4.12 (m, 1H), 3.94 (s, 4H), 3.77 (s, 3H), 3.32-3.41 (m, 2H), 3.15-3.21 (m, 1H), 2.83-2.97 (m, 2H), 1.68-2.04 (m, 8H). LCMS (m+1) 414.

Source