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

HRID 1392900Notes

Reaction equation

HRID 1392900 reaction equation
[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]

Participants

5

Reactant 3

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

Product 1

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

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

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).

Workup

  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

Sources & evidence

ORD record
ord-affb486a76dc4bfc97e8478d0ef6fcac
Source dataset
uspto-grants-2008_03
Patent number
US07345042B2

Reaction notes

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