Isobutyraldehyde → (3R,4S)-3-amino-4-(3-boronopropyl)-1-isobutylpyrrolidine-3-carboxylic acid

HRID 61358

반응식

HRID 61358 반응식
C([NH:4][C@:5]1([C:22](NC(C)(C)C)=[O:23])[C@@H:9]([CH2:10][CH2:11][CH2:12][B:13]2[O:17]C(C)(C)C(C)(C)[O:14]2)[CH2:8][NH:7][CH2:6]1)(=O)C.S([O-])([O-])(=O)=O.[Na+].[Na+].[CH:36](=O)[CH:37]([CH3:39])[CH3:38].C(O[BH-](OC(=O)C)OC(=O)C)(=[O:43])C.[Na+].C(=O)([O-])[O-].[Na+].[Na+]>ClCCCl.C(O)(=O)C>[NH2:4][C@:5]1([C:22]([OH:23])=[O:43])[C@@H:9]([CH2:10][CH2:11][CH2:12][B:13]([OH:14])[OH:17])[CH2:8][N:7]([CH2:36][CH:37]([CH3:39])[CH3:38])[CH2:6]1

참가 물질

8

반응물 5

HCID 6561IsobutyraldehydeHCID 10340Sodium CarbonateHCID 24436Sodium SulfateHCID 5049666Sodium triacetoxyborohydrideHCID 67516451(3R,4S)-3-acetamido-N-tert-butyl-4-(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)propyl)pyrrolidine-3-carboxamide

생성물 1

HCID 57331358(3R,4S)-3-amino-4-(3-boronopropyl)-1-isobutylpyrrolidine-3-carboxylic acid수율 32.3%

시약·촉매·용매 2

HCID 176Acetic Acid촉매HCID 111,2-Dichloroethane용매

실험 절차

A stirred solution of (3R,4S)-3-acetamido-N-tert-butyl-4-(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)propyl)pyrrolidine-3-carboxamide (Example 8, step 4) (198 mg, 0.5 mmol) in anhydrous 1,2-dichloroethane (5 mL) was treated with anhydrous sodium sulfate (1 g) and isobutyraldehyde (0.060 mL, 0.65 mmol), stirred for 2.5 h, then treated with sodium triacetoxyborohydride (212 mg, 1.0 mmol) and glacial acetic acid (2 drops) and stirred for 16 h. Aqueous sodium carbonate (10%, 5 mL) was added and the mixture stirred for a few minutes and extracted with ethyl acetate (30 mL, then 2×10 mL). The combined organic solution was washed with water and saturated aqueous sodium chloride (20 mL each), dried (MgSO4), and concentrated. The crude material was deprotected and isolated using the method described for example 8, step 5 to afford (3R,4S)-3-amino-4-(3-boronopropyl)-1-isobutylpyrrolidine-3-carboxylic acid (44 mg, 26%) as a white semisolid. NMR (D2O) δ 3.90 (m, 1 H), 3.50 (m, 1 H), 2.90-3.20 (m, 4 H), 2.50 (m, 1 H), 1.90 (m, 1 H), 1.50 (m, 1 H), 0.80-1.30 (m, 9 H), 0.65 (m, 2 H). MS (m+1): 273.2; MS (m−H2O+1): 255.2; MS (m−2 H2O+1): 237.2.

후처리

  1. stirringstirred for 16 h
  2. stirringthe mixture stirred for a few minutes
  3. extractionextracted with ethyl acetate (30 mL
  4. washThe combined organic solution was washed with water and saturated aqueous sodium chloride (20 mL each)
  5. dry with materialdried (MgSO4)
  6. concentrationconcentrated
  7. customisolated

출처 및 근거

ORD 기록
ord-51651ed45d7948eab2ad4dac9abb0b93
출처 데이터셋
uspto-grants-2016_09
특허 번호
US09440995B2

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