Hydrochloric Acid → (2S,4S)-1-(tert-butoxycarbonyl)-4-((difluoromethoxy)methyl)pyrrolidine-2-carboxylic acid

HRID 1509739노트

반응식

HRID 1509739 반응식
[F:1][CH:2]([F:21])[O:3][CH2:4][C@@H:5]1[CH2:9][N:8]([C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])[C@H:7]([C:17]([O:19]C)=[O:18])[CH2:6]1.[Li+].[OH-].Cl>C1COCC1.CO>[C:13]([O:12][C:10]([N:8]1[CH2:9][C@@H:5]([CH2:4][O:3][CH:2]([F:1])[F:21])[CH2:6][C@H:7]1[C:17]([OH:19])=[O:18])=[O:11])([CH3:16])([CH3:14])[CH3:15]

참가 물질

6

반응물 3

HCID 313Hydrochloric AcidHCID 3939Lithium HydroxideHCID 69672725(2S,4S)-1-tert-butyl 2-methyl 4-((difluoromethoxy)methyl)pyrrolidine-1,2-dicarboxylate

생성물 1

HCID 69672764(2S,4S)-1-(tert-butoxycarbonyl)-4-((difluoromethoxy)methyl)pyrrolidine-2-carboxylic acid수율 104.3%

시약·촉매·용매 2

HCID 887Methanol용매HCID 8028Tetrahydrofuran용매

실험 절차

To a solution of (2S,4S)-1-tert-butyl 2-methyl 4-((difluoromethoxy)methyl)pyrrolidine-1,2-dicarboxylate (2.41 g, 7.79 mmol) in a mixture of THF (39 mL) and MeOH (15.6 mL) was added LiOH (2.5 M aqueous, 15.6 mL, 38.9 mmol). The resulting solution was stirred at room temperature for 1h. Upon completion by TLC the reaction mixture was acidified with aqueous HCl (1N). The desired product was extracted with CH2Cl2 (3×). The combined organic layers were dried over Na2SO4 and concentrated to provide (2S,4S)-1-(tert-butoxycarbonyl)-4-((difluoromethoxy)methyl)pyrrolidine-2-carboxylic acid (2.4 g, 99%). MS (ESI) m/z 294.96 [M −H]-. 1H-NMR: 400 MHz, (acetone-d6) δ (mixture of rotamers): 6.50 (t, 1H), 4.36-4.17 (m, 1H), 3.93 (d, 2H), 3.77-3.67 (m, 1H), 3.63-3.59 (m, 1H), 3.26-3.12 (m, 1H), 2.72-2.41 (m, 2H), 1.89-1.73 (m, 2H), 1.41 (s, 9H).

후처리

  1. extractionThe desired product was extracted with CH2Cl2 (3×)
  2. dry with materialThe combined organic layers were dried over Na2SO4
  3. concentrationconcentrated

출처 및 근거

ORD 기록
ord-fe3a0881f4d04e56bc638fcb96c4e961
출처 데이터셋
uspto-grants-2015_12
특허 번호
US09221833B2

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