Triethylamine → (3S*,4R*)-4-({Isopropyl-[4-methoxy-3-(3-methoxy-propoxy)-benzoyl]-amino}-methyl)-pyrrolidine-1,3-dicarboxylic acid 1-tert-butyl ester 3-ethyl ester

HRID 1158327Notes

Reaction equation

HRID 1158327 reaction equation
[CH2:1]([O:3][C:4]([C@H:6]1[C@H:10]([CH2:11][NH:12][CH:13]([CH3:15])[CH3:14])[CH2:9][N:8]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:7]1)=[O:5])[CH3:2].[CH3:23][O:24][CH2:25][CH2:26][CH2:27][O:28][C:29]1[CH:30]=[C:31]([CH:35]=[CH:36][C:37]=1[O:38][CH3:39])[C:32](O)=[O:33].O=C1N(P(Cl)(N2CCOC2=O)=O)CCO1.C(N(CC)CC)C>C(Cl)Cl>[CH2:1]([O:3][C:4]([C@H:6]1[C@H:10]([CH2:11][N:12]([CH:13]([CH3:14])[CH3:15])[C:32](=[O:33])[C:31]2[CH:35]=[CH:36][C:37]([O:38][CH3:39])=[C:29]([O:28][CH2:27][CH2:26][CH2:25][O:24][CH3:23])[CH:30]=2)[CH2:9][N:8]([C:16]([O:18][C:19]([CH3:22])([CH3:20])[CH3:21])=[O:17])[CH2:7]1)=[O:5])[CH3:2]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 152842Bis(2-oxo-3-oxazolidinyl)phosphinic chlorideHCID 190395024-Methoxy-3-(3-methoxypropoxy)benzoic acidHCID 68617367HCID 68617367, compound

Product 1

HCID 68617198(3S*,4R*)-4-({Isopropyl-[4-methoxy-3-(3-methoxy-propoxy)-benzoyl]-amino}-methyl)-pyrrolidine-1,3-dicarboxylic acid 1-tert-butyl ester 3-ethyl ester

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A mixture of (3S*,4R*)-4-(isopropylamino-methyl)-pyrrolidine-1,3-dicarboxylic acid 1-tert-butyl ester 3-ethyl ester (2.58 g, 8.2 mmol), 3-(3-methoxy-propoxy)-4-methoxy-benzoic acid (1.93 g, 8.04 mmol), bis(2-oxo-3-oxazolidinyl)phosphinic chloride (2.3 g, 9.02 mmol) and triethylamine (4.57 μL, 32.81 mmol) in CH2Cl2 (50 mL) is refluxed for 2 h and then quenched by the addition of aqueous NaHCO3 solution. The organic layer is separated, and the aqueous phase is extracted 3 times with AcOEt. The combined organic extracts are dried (Na2SO4), and the solvent is removed in vacuo. The crude product is purified by flash chromatography on silica gel (eluent: c-hexane/AcOEt 50:50 to 0:100 and then AcOEt/MeOH 95:5) to give the title product. TLC, Rf (CH2Cl2/MeOH 95:5)=0.3. tR (HPLC, C18 column, 10-100% CH3CN/H2O/5 min, 100% CH3CN/3 min, CH3CN and H2O containing 0.1% TFA, flow: 1.5 mL/min): 5.76 min.

Workup

  1. temperatureis refluxed for 2 h
  2. customquenched by the addition of aqueous NaHCO3 solution
  3. customThe organic layer is separated
  4. extractionthe aqueous phase is extracted 3 times with AcOEt
  5. dry with materialThe combined organic extracts are dried (Na2SO4)
  6. customthe solvent is removed in vacuo
  7. customThe crude product is purified by flash chromatography on silica gel (eluent

Sources & evidence

ORD record
ord-8ae5db3d10214735a89d7698b8eee25e
Source dataset
uspto-grants-2010_10
Patent number
US07807709B2

Reaction notes

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