Tributylstannane → HCID 69529341, compound

HRID 2215947Notes

Reaction equation

HRID 2215947 reaction equation
C([O:4][C:5]1[CH:22]=[CH:21][C:20]2[C@@H:19]3[C@H:10]([C@H:11]4[C@@:15]([CH2:17][C@@H:18]3[F:23])([CH3:16])[CH:14]=[CH:13][CH2:12]4)[C@H:9]([CH3:24])[CH2:8][C:7]=2[CH:6]=1)(=O)C.BrN1C(=[O:31])CCC1=O.C([SnH](CCCC)CCCC)CCC.CC(N=NC(C#N)(C)C)(C#N)C>CS(C)=O.O.C(OCC)(=O)C>[F:23][C@H:18]1[CH2:17][C@@:15]2([CH3:16])[C@@H:11]([CH2:12][C@H:13]([OH:31])[CH2:14]2)[C@H:10]2[C@H:19]1[C:20]1[CH:21]=[CH:22][C:5]([OH:4])=[CH:6][C:7]=1[CH2:8][C@H:9]2[CH3:24]

Participants

8

Reactant 4

HCID 5948TributylstannaneHCID 6547AzobisisobutyronitrileHCID 67184N-bromobutanimideHCID 21057285HCID 21057285, compound

Product 1

HCID 69529341HCID 69529341, compound

Reagents, catalysts & solvents 3

HCID 679Dimethyl SulfoxideSolventHCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

A solution of 1.67 g (5.22 mmol) of 3-acetyloxy-11βfluoro-7α-methylestra-1,3,5(10),16-tetraene in 30 ml of DMSO and 2.4 ml of water is replaced in portions with 1.36 g of N-bromosuccinimide while being stirred at 0° C., the cold bath is removed after the addition of NBS is completed, and it is stirred for 45 more minutes at room temperature. For working-up, the reaction mixture is poured into ice water, extracted with ethyl acetate, the organic phase is washed with water and dried on sodium sulfate. The crude bromohydrin (2.3 g) is then taken up in 25 ml of dry tetrahydrofuran, mixed with 5 ml (18.6 mmol) of tributyl tin hydride, a first spatula tip full of AIBN (a total of 200 mg dispersed over the reaction time), and stirred for 10 hours at a bath temperature of 80° C. under an argon atmosphere. For working-up, it is diluted with ethyl acetate, the organic phase is washed with dilute hydrochloric acid and water and dried on sodium sulfate. For saponification, the crude product is dissolved in 50 ml of methanol and 5 ml of dichloromethane, and it is mixed with 2.0 g of potassium carbonate. The reaction mixture is stirred for 1.5 hours under argon and poured into ice water for working-up. It is made hydrochloric with dilute acid, and it is extracted with ethyl acetate. The organic phase is washed with water and dried on sodium sulfate. The crude product is chromatographed on silica gel (chloroform-tert-butylmethylether, gradient of up to 95:5), yield 1.16 g (75%), melting point 239–240° C. while decomposing, [α]D+96.8° (c 0.51 methanol).

Workup

  1. customthe cold bath is removed
  2. additionafter the addition of NBS
  3. stirringit is stirred for 45 more minutes at room temperature
  4. additionthe reaction mixture is poured into ice water
  5. extractionextracted with ethyl acetate
  6. washthe organic phase is washed with water
  7. customdried on sodium sulfate
  8. stirringstirred for 10 hours at a bath temperature of 80° C. under an argon atmosphere
  9. washthe organic phase is washed with dilute hydrochloric acid and water
  10. customdried on sodium sulfate
  11. dissolutionFor saponification, the crude product is dissolved in 50 ml of methanol
  12. addition5 ml of dichloromethane, and it is mixed with 2.0 g of potassium carbonate
  13. stirringThe reaction mixture is stirred for 1.5 hours under argon
  14. additionpoured into ice water
  15. additionwith dilute acid, and it
  16. extractionis extracted with ethyl acetate
  17. washThe organic phase is washed with water
  18. customdried on sodium sulfate
  19. customThe crude product is chromatographed on silica gel (chloroform-tert-butylmethylether, gradient of up to 95:5), yield 1.16 g (75%), melting point 239–240° C.

Sources & evidence

ORD record
ord-d262b2a599964ace9df5716a139a7e56
Source dataset
uspto-grants-2006_09
Patent number
US07109360B1

Reaction notes

Loading…