Pyrrolidine → HCID 66832625, compound

HRID 579549Notes

Reaction equation

HRID 579549 reaction equation
[C:1]([O:5][C:6]([N:8]([CH3:34])[C:9]([CH2:30][CH2:31][CH:32]=O)([CH2:17][CH2:18][CH2:19][CH2:20][B:21]1[O:25][C:24]([CH3:27])([CH3:26])[C:23]([CH3:29])([CH3:28])[O:22]1)[C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])=[O:7])([CH3:4])([CH3:3])[CH3:2].[NH:35]1[CH2:39][CH2:38][CH2:37][CH2:36]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCCl>[C:1]([O:5][C:6]([N:8]([CH3:34])[C:9]([CH2:30][CH2:31][CH2:32][N:35]1[CH2:39][CH2:38][CH2:37][CH2:36]1)([CH2:17][CH2:18][CH2:19][CH2:20][B:21]1[O:25][C:24]([CH3:26])([CH3:27])[C:23]([CH3:29])([CH3:28])[O:22]1)[C:10]([O:12][C:13]([CH3:14])([CH3:15])[CH3:16])=[O:11])=[O:7])([CH3:2])([CH3:4])[CH3:3]

Participants

5

Reactant 3

HCID 31268PyrrolidineHCID 5049666Sodium triacetoxyborohydrideHCID 86663729HCID 86663729, compound

Product 1

HCID 66832625HCID 66832625, compoundYield 88%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

A solution of tert-butyl 2-(tert-butoxycarbonyl(methyl)amino)-2-(3-oxopropyl)-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)hexanoate (193 mg, 0.40 mmol, 1.0 equiv) and pyrrolidine (43 mg, 0.60 mmol, 1.5 equiv) in 1,2-dichloroethane (2 mL) was treated with sodium triacetoxyborohydride (168 mg, 0.80 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 concentrated under reduced pressure. Purification by flash column chromatography eluting with gradient 1-10% methanol in chloroform gave tert-butyl 2-(tert-butoxycarbonyl(methyl)amino)-2-(3-(pyrrolidin-1-yl)propyl)-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)hexanoate as an oil (186 mg, 88%). Rf 0.35 (10% methanol in dichloromethane). ESI MS found for C29H55BN2O6 m/z [539.4 (M+1)].

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. concentrationconcentrated under reduced pressure
  9. customPurification by flash column chromatography
  10. washeluting with gradient 1-10% methanol in chloroform

Sources & evidence

ORD record
ord-d888efd4e2414c0f9601f8769208b456
Source dataset
uspto-grants-2015_05
Patent number
US09040703B2

Reaction notes

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