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

HRID 61385Notes

Reaction equation

HRID 61385 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.[CH2:29]([N:36](C(OC(C)(C)C)=O)[CH2:37][CH:38]=O)[C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1.C(O[BH-](OC(=O)C)OC(=O)C)(=[O:49])C.[Na+].C(=O)([O-])[O-].[Na+].[Na+]>ClCCCl>[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]([CH2:38][CH2:37][NH:36][CH2:29][C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)[CH2:6]1

Participants

6

Reactant 4

HCID 10340Sodium CarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 10868680tert-butyl benzyl(2-oxoethyl)carbamateHCID 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

Product 1

HCID 57331520(3R,4S)-3-amino-1-(2-(benzylamino)ethyl)-4-(3-boronopropyl)pyrrolidine-3-carboxylic acidYield 64.1%

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-benzyl-N-BOC-glycinaldehyde (0.187 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-1-(2-(benzylamino)ethyl)-4-(3-boronopropyl)pyrrolidine-3-carboxylic acid (112 mg, 49%) as a white solid. NMR (D2O) δ 7.30-7.45 (m, 5 H), 4.21 (s, 2 H), 3.94 (d, 1 H, J=12 Hz, 1 H), 3.84 (t, J=9.5 Hz, 1 H), 3.60-3.75 (m, 3 H), 3.30-3.50 (m, 3 H), 2.50-2.65 (m, 1 H), 1.50-1.65 (m, 1 H), 1.10-1.35 m, 3 H), 0.63-0.73 (m, 2 H). MS (m+1): 350.4; MS (m−H2O+1): 332.1.

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-341a28ad3849489790182b373d04d9f1
Source dataset
uspto-grants-2016_09
Patent number
US09440995B2

Reaction notes

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