N-Ethylbenzylamine → HCID 68618189, compound

HRID 1158419Notes

Reaction equation

HRID 1158419 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]([O:22][CH3:23])=[C:18]([O:24][CH2:25][CH2:26][CH2:27][O:28][CH3:29])[CH:17]=2)[C@H:10]([CH2:34][OH:35])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].ClC(Cl)(O[C:40](=[O:46])OC(Cl)(Cl)Cl)Cl.[CH2:48]([NH:50][CH2:51][C:52]1[CH:57]=[CH:56][CH:55]=[CH:54][CH:53]=1)[CH3:49].C([O-])(O)=O.[Na+]>C(Cl)Cl.CN(C1C=CN=CC=1)C>[C:1]([O:5][C:6]([N:8]1[CH2:12][C@@H:11]([CH2:13][N:14]([CH:31]([CH3:32])[CH3:33])[C:15](=[O:30])[C:16]2[CH:21]=[CH:20][C:19]([O:22][CH3:23])=[C:18]([O:24][CH2:25][CH2:26][CH2:27][O:28][CH3:29])[CH:17]=2)[C@H:10]([CH2:34][O:35][C:40](=[O:46])[N:50]([CH2:51][C:52]2[CH:57]=[CH:56][CH:55]=[CH:54][CH:53]=2)[CH2:48][CH3:49])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

7

Reactant 4

HCID 84352N-EthylbenzylamineHCID 94429TriphosgeneHCID 516892Sodium BicarbonateHCID 59512299(3S,4R)-3-Hydroxymethyl-4-({isopropyl-[4-methoxy-3-(3-methoxy-propoxy)-benzoyl]-amino}-methyl)-pyrrolidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 68618189HCID 68618189, compound

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent2×

Procedure

To a stirred solution of (3S,4R)-3-hydroxymethyl-4-({isopropyl-[4-methoxy-3-(3-methoxy-propoxy)-benzoyl]-amino}-methyl)-pyrrolidine-1-carboxylic acid tert-butyl ester (250 mg, 0.505 mmol) in CH2Cl2 (10 mL) is added triphosgen (56 mg, 0.187 mmol) and DMAP (197 mg, 1.62 mmol). The resulting solution is stirred 30 min before the addition of commercially available N-ethylbenzylamine (113 μL, 0.758 mmol). The mixture is further stirred overnight, then diluted with CH2Cl2 and poured into an aqueous saturated solution of NaHCO3. The layers are separated and the aqueous one extracted twice with CH2Cl2. The combined organic extracts are dried over Na2SO4, filtered and concentrated. The crude material is purified by flash chromatography on silica gel (eluent: CH2Cl2/MeOH 100:0 to 98:2). TLC, Rf (CH2Cl2/MeOH 95:5)=0.2. MS (LC-MS): 655.9 [M+H]+; 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): 6.36 min.

Workup

  1. customThe layers are separated
  2. extractionthe aqueous one extracted twice with CH2Cl2
  3. dry with materialThe combined organic extracts are dried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe crude material is purified by flash chromatography on silica gel (eluent: CH2Cl2/MeOH 100:0 to 98:2)
  7. customtR (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)
  8. custom6.36 min.

Sources & evidence

ORD record
ord-2d66677235564c7c9c31901cf42a8cb5
Source dataset
uspto-grants-2010_10
Patent number
US07807709B2

Reaction notes

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