Phenylacetyl chloride → N-{(3R*,4S*)-1-Benzyl4-[(isopropyl-phenylacetyl-amino)-methyl]-pyrrolidin-3-ylmethyl}-N-isopropyl-4-methoxy-3-(3-methoxy-propoxy)-benzamide

HRID 1158486Notes

Reaction equation

HRID 1158486 reaction equation
[CH2:1]([N:8]1[CH2:12][C@@H:11]([CH2:13][NH:14][CH:15]([CH3:17])[CH3:16])[C@@H:10]([CH2:18][N:19]([CH:36]([CH3:38])[CH3:37])[C:20](=[O:35])[C:21]2[CH:26]=[CH:25][C:24]([O:27][CH3:28])=[C:23]([O:29][CH2:30][CH2:31][CH2:32][O:33][CH3:34])[CH:22]=2)[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(N(CC)CC)C.[C:46]1([CH2:52][C:53](Cl)=[O:54])[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=1.[OH-].[Na+]>CN(C1C=CN=CC=1)C.C(Cl)Cl>[CH2:1]([N:8]1[CH2:12][C@@H:11]([CH2:13][N:14]([CH:15]([CH3:17])[CH3:16])[C:53](=[O:54])[CH2:52][C:46]2[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=2)[C@@H:10]([CH2:18][N:19]([CH:36]([CH3:38])[CH3:37])[C:20](=[O:35])[C:21]2[CH:26]=[CH:25][C:24]([O:27][CH3:28])=[C:23]([O:29][CH2:30][CH2:31][CH2:32][O:33][CH3:34])[CH:22]=2)[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 7679Phenylacetyl chlorideHCID 8471TriethylamineHCID 14798Sodium HydroxideHCID 59512319N-[(3R*,4R*)-1-Benzyl-4-(isopropylamino-methyl)-pyrrolidin-3-ylmethyl]-N-isopropyl-4-methoxy-3-(3-methoxy-propoxy)-benzamide

Product 1

HCID 59512431N-{(3R*,4S*)-1-Benzyl4-[(isopropyl-phenylacetyl-amino)-methyl]-pyrrolidin-3-ylmethyl}-N-isopropyl-4-methoxy-3-(3-methoxy-propoxy)-benzamide

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent2×

Procedure

To a solution of N-[(3R*,4R*)-1-benzyl-4-(isopropylamino-methyl)-pyrrolidin-3-ylmethyl]-N-isopropyl-4-methoxy-3-(3-methoxy-propoxy)-benzamide (0.19 g, 0.36 mmol), triethyl-amine (0.15 mL, 1.09 mmol), and DMAP (0.013 g, 0.11 mmol) in CH2Cl2, is added dropwise phenyl-acetyl chloride (0.058 mL, 0.44 mmol) at 0° C. under a nitrogen atmosphere. The solution is stirred overnight at room temperature. The mixture is added an aqueous solution of NaOH 0.1N (50 mL) and CH2Cl2 (50 mL). The organic layer is separated and the aqueous phase extracted twice with CH2Cl2, dried over MgSO4, filtered, and concentrated in vacuo. The crude product is purified by flash chromatography on silica gel (eluent: CH2Cl2/MeOH 90:10) to give the title product. TLC, Rf (CH2Cl2/MeOH 9:1)=0.23. MS (LC-MS): [M+H]+; 644.4 tR (HPLC, C18 column, 10-100% CH3CN/H2O/5 min, 100% CH3CN/2.5 min, CH3CN and H2O containing 0.1% TFA, flow: 1.5 mL/min): 5.95 min.

Workup

  1. customThe organic layer is separated
  2. extractionthe aqueous phase extracted twice with CH2Cl2
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe crude product is purified by flash chromatography on silica gel (eluent: CH2Cl2/MeOH 90:10)

Sources & evidence

ORD record
ord-a3a44da3faab43cdba812024fbb28899
Source dataset
uspto-grants-2010_10
Patent number
US07807709B2

Reaction notes

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