Potassium bis(trimethylsilyl)amide → 1-[2(R)-[1(S)-(tert-butoxycarbonyl)-2-(3,4,4-trimethyl-2,5-dioxo-1imidazolidinyl)ethyl]-3-cyclopentylpropionyl]piperidine

HRID 429521Notes

Reaction equation

HRID 429521 reaction equation
C[Si]([N-][Si](C)(C)C)(C)C.[K+].BrCN1C(=O)C(C)(C)N(C)C1=O.[C:23]([O:27][C:28]([C@H:30]([C@@H:42]([CH2:51][CH:52]1[CH2:56][CH2:55][CH2:54][CH2:53]1)[C:43]([N:45]1[CH2:50][CH2:49][CH2:48][CH2:47][CH2:46]1)=[O:44])[CH2:31][N:32]1[C:36](=[O:37])[C:35]([CH3:39])([CH3:38])[N:34]([CH3:40])[C:33]1=[O:41])=[O:29])([CH3:26])([CH3:25])[CH3:24]>O1CCCC1>[C:23]([O:27][C:28]([C@@H:30]([C@@H:42]([CH2:51][CH:52]1[CH2:53][CH2:54][CH2:55][CH2:56]1)[C:43]([N:45]1[CH2:46][CH2:47][CH2:48][CH2:49][CH2:50]1)=[O:44])[CH2:31][N:32]1[C:36](=[O:37])[C:35]([CH3:38])([CH3:39])[N:34]([CH3:40])[C:33]1=[O:41])=[O:29])([CH3:24])([CH3:25])[CH3:26]

Participants

5

Reactant 3

HCID 3251421Potassium bis(trimethylsilyl)amideHCID 98050521-[2(R)-[1(R)-(tert-butoxycarbonyl)-2-(3,4,4-trimethyl-2,5-dioxo-1-imidazolidinyl)ethyl]-3cyclopentylpropionyl]piperidineHCID 109334353-Bromomethyl-1,5,5-trimethylhydantoin

Product 1

HCID 233822641-[2(R)-[1(S)-(tert-butoxycarbonyl)-2-(3,4,4-trimethyl-2,5-dioxo-1imidazolidinyl)ethyl]-3-cyclopentylpropionyl]piperidineYield 78%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of 10.7 g of the ester from Example 3 in 50 ml of tetrahydrofuran was added dropwise at −60° to a solution of 8.76 g of potassium bis-trimethylsilylamide in 80 ml of tetrahydrofluran and the mixture was stirred at −60° for 30 min. Subsequently, a solution of 7.76 g of 3-bromomethyl-1,5,5-trimethylhydantoin in 40 ml of tetrahydrofliran was added at −60° and the mixture was stirred at −60° for 30 min. The reaction mixture was washed with semi-saturated sodium chloride solution and with dilute hydrochloric acid, dried, filtered and concentrated, there being obtained 15.11 g of a 9:1 mixture of 1-[2(R)-[1(R)-(tert-butoxycarbonyl)-2-(3,4,4-trimethyl-2,5-dioxo-1-imidazolidinyl)ethyl]-3cyclopentylpropionyl]piperidine and 1-[2(R)-[1(S)-(tert-butoxycarbonyl)-2-(3,4,4-trimethyl-2,5-dioxo-1-imidazolidinyl)ethyl]-3-cyclopentylpropionyl]piperidine (78% yield of pure anti-compound), which was used in the next step without further purification. The mixture can be separated by chromatography on silica gel with hexane/ethyl acetate (1:1).

Workup

  1. stirringthe mixture was stirred at −60° for 30 min
  2. washThe reaction mixture was washed with semi-saturated sodium chloride solution and with dilute hydrochloric acid
  3. customdried
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customthere being obtained

Sources & evidence

ORD record
ord-28ec5c0c3e134616bb2f1027255682e3
Source dataset
uspto-grants-2001_11
Patent number
US06316633B1

Reaction notes

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