Sodium Carbonate → (3R,4S)-3-amino-1-(2-aminoethyl)-4-(3-boronopropyl)pyrrolidine-3-carboxylic acid

HRID 61370

反応式

HRID 61370 の反応式
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+].C([NH:43][CH2:44][CH:45]=O)(OC(C)(C)C)=O.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][NH2:43])[CH2:6]1

参加物

8

反応物 5

HCID 10340Sodium CarbonateHCID 24436Sodium SulfateHCID 4247255tert-butyl N-(2-oxoethyl)carbamateHCID 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

生成物 1

HCID 57331437(3R,4S)-3-amino-1-(2-aminoethyl)-4-(3-boronopropyl)pyrrolidine-3-carboxylic acid収率 49.4%

試薬・触媒・溶媒 2

HCID 176Acetic Acid触媒HCID 111,2-Dichloroethane溶媒

実験手順

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 N-bocaminoacetaldehyde (111 mg, 0.7 mmol), stirred for 3 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-1-(2-aminoethyl)-4-(3-boronopropyl)pyrrolidine-3-carboxylic acid (64 mg, 35%) as a yellow solid. NMR (D2O) δ 3.60-4.00 (m, 4 H), 3.15-3.50 (m, 4 H), 2.60 (m, 1 H), 1.40-1.65 (m, 1 H), 1.10-1.35 (m, 3 H), 0.63-0.73 (m, 2 H). MS (m+1): 260.2; MS (m−H2O+1): 242.3.

後処理

  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

出典と根拠

ORDレコード
ord-2f29f5b36d374ec089bf8c2c0e331cb7
出典データセット
uspto-grants-2016_09
特許番号
US09440995B2

関連ノート

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