p-Tolunitrile → Letrozole

HRID 646657

反応式

HRID 646657 の反応式
[NH:1]1[CH:5]=[N:4][C:3]([Na])=[N:2]1.Br[CH2:8][C:9]1[CH:16]=[CH:15][C:12]([C:13]#[N:14])=[CH:11][CH:10]=1.[C:17]1(C)[CH:22]=[CH:21][C:20]([C:23]#[N:24])=[CH:19][CH:18]=1.FC1C=CC(C#N)=CC=1.C[Si]([N-][Si](C)(C)C)(C)C.[Na+]>C1COCC1.CN(C)C=O>[CH:11]1[C:12]([C:13]#[N:14])=[CH:15][CH:16]=[C:9]([CH:8]([N:2]2[N:1]=[CH:5][N:4]=[CH:3]2)[C:17]2[CH:18]=[CH:19][C:20]([C:23]#[N:24])=[CH:21][CH:22]=2)[CH:10]=1

参加物

8

反応物 5

HCID 7724p-TolunitrileHCID 145174-FluorobenzonitrileHCID 869964-(Bromomethyl)benzonitrileHCID 2724254Sodium bis(trimethylsilyl)amideHCID 178507082HCID 178507082、化合物

生成物 1

HCID 3902Letrozole

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide溶媒HCID 8028Tetrahydrofuran溶媒

反応条件

温度
0 °C

実験手順

A glass reactor was charged with 24.3 grams of 1,2,4-triazolylsodium and 500 grams of dimethylformamide. At a temperature between −10° C. and 0° C., 50 grams of 4-(bromomethyl)benzonitrile (53.2 grams with a purity of about 94 percent by weight, containing about 6 percent by weight of 4-tolunitrile) were added in portions. After stirring at 0° C. for 1 hour, 30.9 grams of 4-fluorobenzonitrile were added, and, while maintaining a temperature of −5° C. to −10° C., 245 grams of a 40 percent solution of sodium bis(trimethylsilyl)amide in THF were added dropwise. After the addition was completed, the reaction was quenched by the addition of 200 grams of 50 percent acetic acid, followed by precipitation of the product by the addition of 1500 grams of water. The resulting suspension was stirred and cooled to about 15° C., and the precipitate was collected and rinsed with water. The wet precipitate was dissolved in 350 grams of dichloromethane, and the solution washed with 250 grams of water. The organic phase was separated, concentrated to a volume of about 200 ml, diluted with 250 grams of toluene, and concentrated to a volume of about 300 ml. The resulting suspension was stirred at ambient temperature for 1 hour, and the precipitate was collected, rinsed with toluene, and dried, yielding 52 grams of crude letrozole product.

後処理

  1. additionwere added in portions
  2. additionwere added dropwise
  3. additionAfter the addition
  4. customthe reaction was quenched by the addition of 200 grams of 50 percent acetic acid
  5. customfollowed by precipitation of the product by the addition of 1500 grams of water
  6. stirringThe resulting suspension was stirred
  7. temperaturecooled to about 15° C.
  8. customthe precipitate was collected
  9. washrinsed with water
  10. dissolutionThe wet precipitate was dissolved in 350 grams of dichloromethane
  11. washthe solution washed with 250 grams of water
  12. customThe organic phase was separated
  13. concentrationconcentrated to a volume of about 200 ml
  14. additiondiluted with 250 grams of toluene
  15. concentrationconcentrated to a volume of about 300 ml
  16. stirringThe resulting suspension was stirred at ambient temperature for 1 hour
  17. customthe precipitate was collected
  18. washrinsed with toluene
  19. customdried

出典と根拠

ORDレコード
ord-b997f925b9a242e8998b0c2e962a05d5
出典データセット
uspto-grants-2010_04
特許番号
US07705159B2

関連ノート

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