Hydrochloric Acid → HCID 59512347, compound

HRID 1158440Notes

Reaction equation

HRID 1158440 reaction equation
[C:1]1([CH2:7][C:8]([OH:10])=O)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[C:11]([O:15][C:16]([N:18]1[CH2:22][C@@H:21]([CH2:23][N:24]([CH:34]([CH3:36])[CH3:35])[C:25]([O:27][CH2:28][CH2:29][Si:30]([CH3:33])([CH3:32])[CH3:31])=[O:26])[C@H:20]([CH2:37][NH:38][CH:39]2[CH2:41][CH2:40]2)[CH2:19]1)=[O:17])([CH3:14])([CH3:13])[CH3:12].C(N(CC)CC)C.O.ON1C2N=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC.Cl>C(Cl)Cl>[C:11]([O:15][C:16]([N:18]1[CH2:22][C@@H:21]([CH2:23][N:24]([CH:34]([CH3:35])[CH3:36])[C:25]([O:27][CH2:28][CH2:29][Si:30]([CH3:32])([CH3:31])[CH3:33])=[O:26])[C@H:20]([CH2:37][N:38]([CH:39]2[CH2:40][CH2:41]2)[C:8](=[O:10])[CH2:7][C:1]2[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=2)[CH2:19]1)=[O:17])([CH3:13])([CH3:14])[CH3:12]

Participants

8

Reactant 6

HCID 313Hydrochloric AcidHCID 999Phenylacetic AcidHCID 8471TriethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 219174661-Hydroxy-7-azabenzotriazol hydrateHCID 59512461HCID 59512461, compound

Product 1

HCID 59512347HCID 59512347, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of phenylacetic acid (1.45 g, 10.53 mmol) and (3R,4S)-3-cyclopropylaminomethyl-4-{[isopropyl-(2-trimethylsilanyl-ethoxycarbonyl)-amino]-methyl}-pyrrolidine-1-carboxylic acid tert-butyl ester (3.2 g, 7.022 mmol) in CH2Cl2 (10 mL), are added triethylamine (1.47 mL, 10.53 mmol) and 1-hydroxy-7-azabenzotriazol hydrate (1.46 g, 10.53 mmol) followed 15 min later by N-(3-dimethylaminopropyl)-N′-ethyl-carbodiimide hydrochloride (3.06 g, 15.78 mmol). The resulting mixture is stirred for 2 days at RT, then diluted with CH2Cl2 and poured into an aqueous 2M HCl solution. The layers are separated and the aqueous one extracted twice with CH2Cl2. The combined organic extracts are neutralized with an aqueous saturated solution of NaHCO3, dried over Na2SO4, filtered and concentrated. The crude product is purified by flash chromatography on silica gel (eluent: hexane/AcOEt 2:1). TLC, Rf (hexane/AcOEt 1:1)=0.42. MS (LC-MS): 574.2 [M+H]+; tR (HPLC, C18 column, 20-100% CH3CN/H2O/6 min, 100% CH3CN/1.5 min, CH3CN and H2O containing 0.1% TFA, flow: 1 mL/min): 6.49 min.

Workup

  1. customThe layers are separated
  2. extractionthe aqueous one extracted twice with CH2Cl2
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe crude product is purified by flash chromatography on silica gel (eluent: hexane/AcOEt 2:1)
  7. customtR (HPLC, C18 column, 20-100% CH3CN/H2O/6 min, 100% CH3CN/1.5 min, CH3CN and H2O containing 0.1% TFA, flow: 1 mL/min)
  8. custom6.49 min.

Sources & evidence

ORD record
ord-f7b72a773d3d40648c921cf21ddc5b14
Source dataset
uspto-grants-2010_10
Patent number
US07807709B2

Reaction notes

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