Pyrrolidine → 2-Tert-butoxycarbonylamino-2-(2-pyrrolidin-yl-ethyl)-6-(4,4,5,5-tetramethyl-[1,3,2]-dioxaborolan-2-yl)-hexanoic acid ethyl ester

HRID 579492Notes

Reaction equation

HRID 579492 reaction equation
[CH2:1]([O:3][C:4](=[O:30])[C:5]([NH:22][C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])([CH2:19][CH:20]=O)[CH2:6][CH2:7][CH2:8][CH2:9][B:10]1[O:14][C:13]([CH3:16])([CH3:15])[C:12]([CH3:18])([CH3:17])[O:11]1)[CH3:2].[NH:31]1[CH2:35][CH2:34][CH2:33][CH2:32]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCCl>[CH2:1]([O:3][C:4](=[O:30])[C:5]([NH:22][C:23]([O:25][C:26]([CH3:29])([CH3:27])[CH3:28])=[O:24])([CH2:19][CH2:20][N:31]1[CH2:35][CH2:34][CH2:33][CH2:32]1)[CH2:6][CH2:7][CH2:8][CH2:9][B:10]1[O:14][C:13]([CH3:15])([CH3:16])[C:12]([CH3:18])([CH3:17])[O:11]1)[CH3:2]

Participants

5

Reactant 3

HCID 31268PyrrolidineHCID 5049666Sodium triacetoxyborohydrideHCID 866637142-tert-Butoxycarbonylamino-2-(2-oxo-ethyl)-6-(4,4,5,5-tetramethyl-[1,3,2]-dioxaborolan-2-yl)-hexanoic acid ethyl ester

Product 1

HCID 668330942-Tert-butoxycarbonylamino-2-(2-pyrrolidin-yl-ethyl)-6-(4,4,5,5-tetramethyl-[1,3,2]-dioxaborolan-2-yl)-hexanoic acid ethyl esterYield 83%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

A solution of 2-tert-Butoxycarbonylamino-2-(2-oxo-ethyl)-6-(4,4,5,5-tetramethyl-[1,3,2]-dioxaborolan-2-yl)-hexanoic acid ethyl ester (100 mg, 0.23 mmol, 1.0 equiv.) and pyrrolidine (21 mg, 0.29 mmol, 1.2 equiv.) in 1,2-dichloroethane (0.5 mL) was treated with sodium triacetoxyborohydride (125 mg, 0.59 mmol) in one portion. After stirring at room temperature overnight, the reaction mixture was quenched with saturated aqueous NaHCO3 (1 mL) and stirred for an additional 5 min. The resulting mixture was added to a separatory funnel, diluted with saturated aqueous NaCl (5 mL) and extracted with dichloromethane (2×10 mL). The organic layer was dried over MgSO4, filtered and concentration under reduced pressure. Purification by flash column chromatography eluting with 5% methanol in chloroform to give 2-tert-butoxycarbonylamino-2-(2-pyrrolidin-yl-ethyl)-6-(4,4,5,5-tetramethyl-[1,3,2]-dioxaborolan-2-yl)-hexanoic acid ethyl ester as a pale yellow oil (92 mg, 83%). Rf 0.32 (10% methanol in dichloromethane); 1H NMR (CDCl3, 300 MHz) δ 5.67 (br, s, NH, 1H), 4.19 (m, 2H), 2.46-2.82 (m, 6H), 2.18 (m, 2H), 1.88 (m, 3H), 1.76 (m, 2H), 1.42 (s, 9H), 1.26-1.41 (m, 3H), 1.28 (t, J=7.0 Hz, 3H), 1.22 (s, 12H), 1.06 (m, 1H) and 0.73 (t, J=7.5 Hz, 2H).

Workup

  1. customthe reaction mixture was quenched with saturated aqueous NaHCO3 (1 mL)
  2. stirringstirred for an additional 5 min
  3. additionThe resulting mixture was added to a separatory funnel
  4. additiondiluted with saturated aqueous NaCl (5 mL)
  5. extractionextracted with dichloromethane (2×10 mL)
  6. dry with materialThe organic layer was dried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentration under reduced pressure
  9. customPurification by flash column chromatography
  10. washeluting with 5% methanol in chloroform

Sources & evidence

ORD record
ord-f2683996498f41a19ef54398d6e983ad
Source dataset
uspto-grants-2015_05
Patent number
US09040703B2

Reaction notes

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