L-Alaninol → HCID 58743044、化合物

HRID 1522852ノート

反応式

HRID 1522852 の反応式
CS(O[CH2:6][C@H:7]([CH3:15])[CH2:8][CH2:9]OS(C)(=O)=O)(=O)=O.[NH2:16][C@@H:17]([CH3:20])[CH2:18][OH:19]>C(Cl)Cl.C([O-])([O-])=O.[K+].[K+].O>[CH3:15][C@@H:7]1[CH2:8][CH2:9][N:16]([C@@H:17]([CH3:20])[CH2:18][OH:19])[CH2:6]1

参加物

6

反応物 2

HCID 80307L-AlaninolHCID 10858216HCID 10858216、化合物2 回

生成物 1

HCID 58743044HCID 58743044、化合物収率 86.8%

試薬・触媒・溶媒 3

HCID 962Water溶媒HCID 6344Dichloromethane溶媒HCID 11430Potassium Carbonate溶媒

実験手順

(R)-2-Methylbutane-1,4-diyl dimethanesulfonate (37.5 g, 0.144 mol, from step 2 of Intermediate 11) was added to neat (S)-2-aminopropan-1-ol (54.8 g, 0.730 mol). The mixture was stirred in a room temperature water bath to minimize the exotherm. After 24 h, the reaction was diluted with DCM (150 mL), sat'd K2CO3 solution (150 mL), and just enough water (60 mL) to dissolve the resulting ppt. The organic layer was separated, and the aqueous layer was extracted with DCM (150 mL). The organic layers were combined, dried (Na2SO4), filtered, concentrated, and purified by silica gel chromatography (10:7; ethyl acetate:hexanes→10:7:2:1; ethyl acetate:hexanes:methanol:triethylamine) to give (S)-2-((R)-3-methylpyrrolidin-1-yl)propan-1-ol (17.9 g) as a pale yellow oil. 1H NMR (400 MHz, DMSO-d6): δ 4.33 (t, 1H), 3.48 (m, 1H), 3.18 (m, 1H), 2.79 (dd, 1H), 2.58 (m, 1H), 2.48 (m, 1H), 2.26 (m, 1H), 2.08 (m, 1H), 2.01 (dd, 1H), 1.88 (m, 1H), 1.20 (m, 1H), 0.98 (d, 3H), 0.96 (d, 3H); LCMS: 144.3 (M+H)+.

後処理

  1. dissolutionto dissolve the resulting ppt
  2. customThe organic layer was separated
  3. extractionthe aqueous layer was extracted with DCM (150 mL)
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. custompurified by silica gel chromatography (10:7; ethyl acetate:hexanes→10:7:2:1; ethyl acetate:hexanes:methanol:triethylamine)

出典と根拠

ORDレコード
ord-1cf0773b4f6546d8aa5ad32f91f1f8c0
出典データセット
uspto-grants-2015_07
特許番号
US09078871B2

反応ノート

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