Acetic Acid → 4-((S)-2-Hydroxymethyl-pyrrolidin-1-yl)-piperidine-1-carboxylic acid tert-butyl ester

HRID 545332노트

반응식

HRID 545332 반응식
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C:11](=O)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[NH:15]1[CH2:19][CH2:18][CH2:17][C@H:16]1[CH2:20][OH:21].C(O)(=O)C.C(=O)([O-])[O-].[Na+].[Na+]>CCO.ClCCCl>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([N:15]2[CH2:19][CH2:18][CH2:17][C@H:16]2[CH2:20][OH:21])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

참가 물질

7

반응물 4

HCID 176Acetic AcidHCID 10340Sodium CarbonateHCID 640091L-ProlinolHCID 735900tert-Butyl 4-oxopiperidine-1-carboxylate

생성물 1

HCID 574411334-((S)-2-Hydroxymethyl-pyrrolidin-1-yl)-piperidine-1-carboxylic acid tert-butyl ester수율 73%

시약·촉매·용매 2

HCID 111,2-Dichloroethane용매HCID 702Ethanol용매

실험 절차

A solution of 10.0 g (50.2 mmol) of 4-oxo-piperidine-1-carboxylic acid tert-butyl ester and 6.00 ml=6.15 g (60.2 mmol) of (S)-(−)-pyrrolidin-2-yl-methanol in 100.0 ml of EtOH was treated with 100.0 ml of 1,2-dichloroethane, followed by 7.53 ml (60.2 mmol) of borane-pyridine complex (8 molar). Then, 7.46 ml=7.84 g (130.5 mmol) of acetic acid was added to this solution. After stirring at RT for 16 hours, the reaction mixture was poured into crashed ice; then, the pH was adjusted to 9-10 with sodium carbonate solution and the mixture was extracted twice with EtOAc; the combined organic phases were washed with water, dried over MgSO4, filtered and evaporated. The residue was purified by flash column chromatography (CH2Cl2/MeOH 1:0 to 9:1) to give 10.4 g (73%) of the title compound as light yellow oil. MS: 285.1 (MH+).

후처리

  1. additionthe reaction mixture was poured
  2. extractionthe mixture was extracted twice with EtOAc
  3. washthe combined organic phases were washed with water
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. customevaporated
  7. customThe residue was purified by flash column chromatography (CH2Cl2/MeOH 1:0 to 9:1)

출처 및 근거

ORD 기록
ord-ff5891ed8a98488db371610b278a48b2
출처 데이터셋
uspto-grants-2011_05
특허 번호
US07935707B2

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