tert-Butyl 4-oxopiperidine-1-carboxylate → 1-tert-butoxycarbonyl-4-{4-[1 (S)-(4-bromophenyl)-ethyl]-3(R)-methylpiperazin-1-yl}-piperidine

HRID 1392900ノート

反応式

HRID 1392900 の反応式
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([N:10]2[CH2:15][CH2:14][NH:13][CH2:12][CH:11]2[CH3:16])[CH3:9])=[CH:4][CH:3]=1.[C:17]([N:24]1[CH2:29][CH2:28][C:27](=O)[CH2:26][CH2:25]1)([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C(Cl)Cl>[C:20]([O:19][C:17]([N:24]1[CH2:29][CH2:28][CH:27]([N:13]2[CH2:14][CH2:15][N:10]([C@H:8]([C:5]3[CH:6]=[CH:7][C:2]([Br:1])=[CH:3][CH:4]=3)[CH3:9])[C@H:11]([CH3:16])[CH2:12]2)[CH2:26][CH2:25]1)=[O:18])([CH3:23])([CH3:21])[CH3:22]

参加物

5

反応物 3

HCID 735900tert-Butyl 4-oxopiperidine-1-carboxylateHCID 5049666Sodium triacetoxyborohydrideHCID 649307071-[1-(4-Bromo-phenyl)-ethyl]-2-methyl-piperazine

生成物 1

HCID 154070791-tert-butoxycarbonyl-4-{4-[1 (S)-(4-bromophenyl)-ethyl]-3(R)-methylpiperazin-1-yl}-piperidine

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

The product of step 4 was stirred for 20 h. at RT with N-Boc-4-piperidinone (4.32 g), HOAC (1.15 ml), CH2Cl2 (80 ml) and sodium triacetoxy-borohydride (NaBH(OAc)3) (8.3 g). Thereafter the reaction was quenched with excess aqueous Na2CO3 solution slowly and stirred for 0.5 h. The organic layer was separated and filtered through a pad of silca gel, washing with 10:1 CH2Cl2-Et2O to elute all of the product. The filtate was evaporated and dissolved in Et2O (100 ml). To this was added dropwise a 4M solution of HCl in 1,4-dioxane (10 ml). The solids were collected, washed with Et2O, and stirred with CH2Cl2 and excess aqueous NaOH. The organic phase was dried over K2CO3 and evaporated to obtain 1-tert-butoxycarbonyl-4-{4-[1 (S)-(4-bromophenyl)-ethyl]-3(R)-methylpiperazin-1-yl}-piperidine (5.45 g).

後処理

  1. customThereafter the reaction was quenched with excess aqueous Na2CO3 solution slowly
  2. customThe organic layer was separated
  3. filtrationfiltered through a pad of silca gel
  4. washwashing with 10:1 CH2Cl2-Et2O
  5. washto elute all of the product
  6. customThe filtate was evaporated
  7. dissolutiondissolved in Et2O (100 ml)
  8. additionTo this was added dropwise a 4M solution of HCl in 1,4-dioxane (10 ml)
  9. customThe solids were collected
  10. washwashed with Et2O
  11. stirringstirred with CH2Cl2 and excess aqueous NaOH
  12. dry with materialThe organic phase was dried over K2CO3
  13. customevaporated

出典と根拠

ORDレコード
ord-affb486a76dc4bfc97e8478d0ef6fcac
出典データセット
uspto-grants-2008_03
特許番号
US07345042B2

反応ノート

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