Tetrahydrofuran → 4-(Tert-butoxycarbonylamino)-2-(4-chlorobenzyl)butanoic acid

HRID 79559

反応式

HRID 79559 の反応式
[Li+].C[Si]([N-][Si](C)(C)C)(C)C.[O:11]=[C:12]1[CH2:16][CH2:15][CH2:14][N:13]1[C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18].Br[CH2:25][C:26]1[CH:31]=[CH:30][C:29]([Cl:32])=[CH:28][CH:27]=1.C1C[O:36]CC1>>[C:20]([O:19][C:17]([NH:13][CH2:14][CH2:15][CH:16]([CH2:25][C:26]1[CH:31]=[CH:30][C:29]([Cl:32])=[CH:28][CH:27]=1)[C:12]([OH:36])=[O:11])=[O:18])([CH3:23])([CH3:22])[CH3:21]

参加物

5

反応物 4

HCID 8028Tetrahydrofuran3 回HCID 693291-(Bromomethyl)-4-chlorobenzeneHCID 3790001-Pyrrolidinecarboxylic acid, 2-oxo-, 1,1-dimethylethyl esterHCID 2733832Lithium Hexamethyldisilazide2 回

生成物 1

HCID 687376094-(Tert-butoxycarbonylamino)-2-(4-chlorobenzyl)butanoic acid収率 9.4%

実験手順

LHMDS (28.3 mL, 28.3 mmol) was diluted into THF (90 mL) and cooled to −78° C. tert-Butyl 2-oxopyrrolidine-1-carboxylate (5.00 g, 27.0 mmol) was dissolved into THF (35 mL) and added to the LHMDS over a 5 minute period at −78° C. The reaction was allowed to stir for 45 minutes, and then a THF (35 mL) solution of 1-(bromomethyl)-4-chlorobenzene (5.82 g, 28.3 mmol, 1.05 equiv) was added. The reaction was allowed to stir at −78° C. for 1 hour, and then warmed to room temperature over 3 hours. The mixture was quenched with the addition of a 3M LiOH solution (90 mL) and stirred for 48 hours at room temperature. The reaction was then diluted with water and washed with ethyl acetate. The aqueous layer was acidified with 3M HCl and extracted several times with ethyl acetate. The combined organic fractions were washed with water, dried over MgSO4, filtered, and concentrated to give the crude product. The crude product was purified by column chromatography (60:40 hexanes:ethyl acetate) to give 4-(tert-butoxycarbonylamino)-2-(4-chlorobenzyl)butanoic acid (0.84 g, 9.4%).

後処理

  1. stirringto stir at −78° C. for 1 hour
  2. customThe mixture was quenched with the addition of a 3M LiOH solution (90 mL)
  3. stirringstirred for 48 hours at room temperature
  4. additionThe reaction was then diluted with water
  5. washwashed with ethyl acetate
  6. extractionextracted several times with ethyl acetate
  7. washThe combined organic fractions were washed with water
  8. dry with materialdried over MgSO4
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customto give the crude product
  12. customThe crude product was purified by column chromatography (60:40 hexanes:ethyl acetate)

出典と根拠

ORDレコード
ord-3343d5e3f3764eea883a55b15489d232
出典データセット
uspto-grants-2014_09
特許番号
US08841304B2

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