Water → (3S,4R)-3-Hydroxymethyl-4-({isopropyl-[1-(3-methoxy-propyl)-3-methyl-1H-indole-6-carbonyl]-amino}-methyl)-pyrrolidine-1-carboxylic acid tert-butyl ester

HRID 1158382

Reaction equation

HRID 1158382 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:12][C@@H:11]([CH2:13][N:14]([CH:31]([CH3:33])[CH3:32])[C:15](=[O:30])[C:16]2[CH:21]=[CH:20][C:19](OC)=[C:18](OCCCOC)[CH:17]=2)[C@H:10]([C:34](C)(C)[O:35][SiH2]C(C)(C)C)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].O.[F-].C([N+:47]([CH2:52][CH3:53])([CH2:50][CH3:51])CC)C.O.C[CH2:56][O:57][C:58](C)=O.[CH3:61]C#N>>[C:1]([O:5][C:6]([N:8]1[CH2:12][C@@H:11]([CH2:13][N:14]([CH:31]([CH3:33])[CH3:32])[C:15]([C:16]2[CH:17]=[C:18]3[C:19]([C:53]([CH3:61])=[CH:52][N:47]3[CH2:50][CH2:51][CH2:56][O:57][CH3:58])=[CH:20][CH:21]=2)=[O:30])[C@H:10]([CH2:34][OH:35])[CH2:9]1)=[O:7])([CH3:2])([CH3:3])[CH3:4]

Participants

6

Reactant 5

HCID 962WaterHCID 6342AcetonitrileHCID 8857Ethyl AcetateHCID 16211652Tetraethylammonium fluoride hydrateHCID 131728362(3S*,4R*)-3-(tert-Butyl-dimethyl-silanyloxymethyl)-4-({isopropyl-[4-methoxy-3-(3-methoxy-propoxy)-benzoyl]-amino}-methyl)-pyrrolidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 68616183(3S,4R)-3-Hydroxymethyl-4-({isopropyl-[1-(3-methoxy-propyl)-3-methyl-1H-indole-6-carbonyl]-amino}-methyl)-pyrrolidine-1-carboxylic acid tert-butyl ester

Procedure

To a solution of (3S,4R)-3-(tert-butyl-dimethyl-silanyloxymethyl)-4-({isopropyl-[4-methoxy-3-(3-methoxy-propoxy)-benzoyl]-amino}-methyl)-pyrrolidine-1-carboxylic acid tert-butyl ester (13.8 g, 22 mmol) in MeCN (350 mL) is added tetraethylammonium fluoride hydrate (6.6 g, 44 mmol) under a nitrogen atmosphere. The reaction mixture is refluxed for 3 h. Water and AcOEt are added, the layers are separated and the aqueous one extracted twice with AcOEt. The combined organic extracts are dried (Na2SO4), filtered and the solvent is removed in vacuo. The crude product is purified by flash chromatography on silica gel (eluent: CH2Cl2/MeOH 100:0 to 90:10) to give the title product. TLC, Rf (CH2Cl2/MeOH 95:5)=0.2. MS (LC-MS): 402.2 [M+H-Boc]+; tR (HPLC, Macherey-Nagel Nucleosil C18 column, 10-100% CH3CN/H2O/5 min, 100% CH3CN/3 min, CH3CN and H2O containing 0.1% TFA, flow: 1.5 mL/min): 6.85 min.

Workup

  1. temperatureThe reaction mixture is refluxed for 3 h
  2. customthe layers are separated
  3. extractionthe aqueous one extracted twice with AcOEt
  4. dry with materialThe combined organic extracts are dried (Na2SO4)
  5. filtrationfiltered
  6. customthe solvent is removed in vacuo
  7. customThe crude product is purified by flash chromatography on silica gel (eluent: CH2Cl2/MeOH 100:0 to 90:10)

Sources & evidence

ORD record
ord-f7423f264218478e84b5fbba226b9e50
Source dataset
uspto-grants-2010_10
Patent number
US07807709B2

Linked notes

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