Fluorination process

• US 7,572,928 B2
• Filed: 12/02/2005
• Issued: 08/11/2009
• Est. Priority Date: 12/02/2005
• Status: Expired due to Fees

• Current Assignee: Isis Innovation Limited
• Original Assignee: Isis Innovation Limited
• Inventors: Gouverneur, Veronique
• Primary Examiner(s): Price; Elvis O
• Application Number:
  US11/292,308
• Publication Number:
  US 20070142632A1
• Time in Patent Office: 1,348 Days
• Field of Search: 556/441, 556/476
• US Class Current: 556/441
• CPC Class Codes: C07F 7/083 Syntheses without formation of a Si-C bond

Abstract

Compounds of formula (II), (IIIa) or (IIIb)

(variables are described in the specification) are prepared by fluorination of β,γ-unsaturated alkyl silanes. These compounds are useful as building blocks in the pharmaceutical industry.

Claims

1. A process for producing a compound of formula (IIIa)

2. A process according to claim 1 wherein, the source of electrophilic fluorine is [1-(chloromethyl)-4-fluoro-1,4-diazoniabicyclo[2.2.2]octane bis(tetrafluoroborate)].

3. A process according to claim 1 wherein L is a C₁alkylene or C₂alkylene group and Nu is —

C(O)O—

, or L is a C₂alkylene or C₃alkylene group and Nu is —

O—

.

4. A process according to claim 1 wherein L is unsubstituted.

5. A process according to claim 1 wherein R⁴ is H or -alk-H and (i) L is an ethylene group which is unsubstituted or substituted by one or more of R¹⁰, aryl and -alk-aryl and Nu is —

O—

;

or (ii) L is a methylene group which is unsubstituted or substituted by one or more of R¹⁰, aryl and -alk-aryl and Nu is —

C(O)O—

.

6. A process according to claim 5 wherein R⁴ is H.

7. A process according to claim 5 wherein either (i) L is an ethylene group substituted by a phenylethyl group alpha to Nu and Nu is —

O—

, or (ii) L is an unsubstituted methylene or ethylene group and Nu is —

C(O)O—

.

8. A process according to claim 7 wherein SiR¹R²R³ is an SiⁱPr₃ group.

9. A process according to claim 1 wherein said aryl groups contain from 6 to 10 carbon atoms and are unsubstituted or substituted with one or two substituents, which substituents are selected from the group consisting of nitro, halo, C_1-6alkyl and C_1-6alkoxy.

10. A process according to claim 1 wherein R¹, R² and R³ are each selected from methyl, ethyl, t-butyl, i-propyl and phenyl.

11. A process according to claim 1 wherein SiR¹R²R³ is SiMe₂^tBu, SiⁱPr₃, SiPhⁱPr₂, Si^tBuPh₂ or SiPh₃.

12. A process according to claim 1 wherein R⁴ is selected from hydrogen and C_1-6alkyl.