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

HRID 590730Notes

Reaction equation

HRID 590730 reaction equation
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.[Cl:29][C:30]1[CH:31]=[C:32]([CH:45]=[CH:46][C:47]=1[Cl:48])[CH2:33][N:34](C(OC(C)(C)C)=O)[CH2:35][CH:36]=O.C(O[BH-](OC(=O)C)OC(=O)C)(=[O:51])C.[Na+].C(=O)([O-])[O-].[Na+].[Na+]>ClCCCl>[NH2:4][C@:5]1([C:22]([OH:23])=[O:51])[C@@H:9]([CH2:10][CH2:11][CH2:12][B:13]([OH:14])[OH:17])[CH2:8][N:7]([CH2:36][CH2:35][NH:34][CH2:33][C:32]2[CH:45]=[CH:46][C:47]([Cl:48])=[C:30]([Cl:29])[CH:31]=2)[CH2:6]1

Participants

6

Reactant 4

HCID 10340Sodium CarbonateHCID 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-carboxamideHCID 86665786N-(3,4-dichlorobenzyl)-N-BOC-glycinaldehyde

Product 1

HCID 57331521(3R,4S)-3-amino-4-(3-boronopropyl)-1-(2-(3,4-dichlorobenzylamino)ethyl)pyrrolidine-3-carboxylic acidYield 53.1%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

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) and N-(3,4-dichlorobenzyl)-N—BOC-glycinaldehyde (0.240 g, 0.75 mmol) in anhydrous 1,2-dichloroethane (5 mL) was stirred at room temperature for 30 min, then cooled by ice bath and treated with sodium triacetoxyborohydride (212 mg, 1.0 mmol) and stirred for 3 h at room temperature. 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 brine (20 mL each), dried (MgSO4), and concentrated in vacuo. 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-(2-(3,4-dichlorobenzylamino)ethyl)pyrrolidine-3-carboxylic acid (111 mg, 42%) as a white solid. NMR (D2O) δ 7.50-7.60 (m, 2 H), 7.28 (dd, J1=8.5 Hz, J2=2 Hz, 1 H), 4.20 (s, 2 H), 3.94 (d, J=12 Hz, 1 H), 3.84 (dd, J1=11.5 Hz, J2=8 Hz, 1 H), 3.60-3.75 (m, 3 H), 3.30-3.45 (m, 3 H), 2.50-2.65 (m, 1 H), 1.50-1.65 (m, 1 H), 1.10-1.35 (m, 3 H), 0.62-0.72 (m, 2 H). MS (m+1): 417.9; MS (m−H2O+1): 400.3.

Workup

  1. temperaturecooled by ice bath
  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 brine (20 mL each)
  5. dry with materialdried (MgSO4)
  6. concentrationconcentrated in vacuo
  7. customisolated

Sources & evidence

ORD record
ord-a3f3b96453b341f0ae283ec6db506d74
Source dataset
uspto-grants-2016_01
Patent number
US09233985B2

Reaction notes

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