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

HRID 1517063ノート

反応式

HRID 1517063 の反応式
[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]

参加物

7

反応物 4

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

生成物 1

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

試薬・触媒・溶媒 2

HCID 111,2-Dichloroethane溶媒HCID 702Ethanol溶媒

実験手順

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+).

後処理

  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)

出典と根拠

ORDレコード
ord-413728481f75433bb227ed4050a75a5b
出典データセット
uspto-grants-2012_07
特許番号
US08227613B2

反応ノート

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