Sodium Carbonate → (3R,4S)-3-amino-4-(3-boronopropyl)-1-(3-(4-chlorophenyl)propyl)pyrrolidine-3-carboxylic acid

HRID 590712

반응식

HRID 590712 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+].[Cl:36][C:37]1[CH:42]=[CH:41][C:40]([CH2:43][CH2:44][CH:45]=O)=[CH:39][CH:38]=1.C(O[BH-](OC(=O)C)OC(=O)C)(=[O:49])C.[Na+].C(=O)([O-])[O-].[Na+].[Na+]>ClCCCl.C(O)(=O)C>[NH2:4][C@:5]1([C:22]([OH:23])=[O:49])[C@@H:9]([CH2:10][CH2:11][CH2:12][B:13]([OH:14])[OH:17])[CH2:8][N:7]([CH2:45][CH2:44][CH2:43][C:40]2[CH:41]=[CH:42][C:37]([Cl:36])=[CH:38][CH:39]=2)[CH2:6]1

참가 물질

8

반응물 5

HCID 10340Sodium CarbonateHCID 24436Sodium SulfateHCID 5049666Sodium triacetoxyborohydrideHCID 115356223-(4-Chlorophenyl)propanalHCID 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 57331435(3R,4S)-3-amino-4-(3-boronopropyl)-1-(3-(4-chlorophenyl)propyl)pyrrolidine-3-carboxylic acid수율 45.7%

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 3-(4-chlorophenyl)propionaldehyde (118 mg, 0.7 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 18 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-(3-(4-chlorophenyl)propyl)pyrrolidine-3-carboxylic acid (84.3 mg, 38%) as a white powder. NMR (D2O) 7.25 (d, J=8 Hz, 2 H), 7.13 (d, J=8 Hz, 2 H), 3.75-4.10 (m, 2 H), 3.40-3.60 (m, 1 H), 3.10-3.30 (m, 3 H), 2.60 (t, J=7 Hz, 2 H), 2.40-2.55 (m, 1 H), 1.85-2.00 (m, 2 H), 1.50-1.65 (m, 1 H), 1.10-1.40 (m, 3 H), 0.60-0.70 (m, 2 H). MS (m+1): 369.1; MS (m−H2O+1): 351.2.

후처리

  1. stirringstirred for 18 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-9a6591eb41344bec950a310eabd55b5a
출처 데이터셋
uspto-grants-2016_01
특허 번호
US09233985B2

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