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

HRID 1158491Notes

Reaction equation

HRID 1158491 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:12][C@@H:11]([CH2:13][NH:14][CH3:15])[C@H:10]([CH2:16][N:17]([CH:34]([CH3:36])[CH3:35])[C:18](=[O:33])[C:19]2[CH:24]=[CH:23][C:22]([O:25][CH3:26])=[C:21]([O:27][CH2:28][CH2:29][CH2:30][O:31][CH3:32])[CH:20]=2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[C:37]1([CH2:43][S:44](Cl)(=[O:46])=[O:45])[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1.C(N(CC)CC)C.C([O-])(O)=O.[Na+]>C(Cl)Cl>[C:1]([O:5][C:6]([N:8]1[CH2:12][C@@H:11]([CH2:13][N:14]([CH3:15])[S:44]([CH2:43][C:37]2[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=2)(=[O:46])=[O:45])[C@H:10]([CH2:16][N:17]([CH:34]([CH3:36])[CH3:35])[C:18](=[O:33])[C:19]2[CH:24]=[CH:23][C:22]([O:25][CH3:26])=[C:21]([O:27][CH2:28][CH2:29][CH2:30][O:31][CH3:32])[CH:20]=2)[CH2:9]1)=[O:7])([CH3:3])([CH3:4])[CH3:2]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 74740Phenylmethanesulfonyl chlorideHCID 516892Sodium BicarbonateHCID 59512501(3R*,4R*)-3-({Isopropyl-[4-methoxy-3-(3-methoxy-propoxy)-benzoyl]-amino}-methyl)-4-methylaminomethyl-pyrrolidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 68643106(3R*,4S*)-3-({isopropyl-[4-methoxy-3-(3-methoxy-propoxy)-benzoyl]-amino}-methyl)-4-[(methyl-phenylmethanesulfonyl-amino)-methyl]-pyrrolidine-1-carboxylic acid tert-butyl ester

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of (3R*,4R*)-3-({isopropyl-[4-methoxy-3-(3-methoxy-propoxy)-benzoyl]-amino}-methyl)-4-methylaminomethyl-pyrrolidine-1-carboxylic acid tert-butyl ester (89 mg, 0.175 mmol) in CH2Cl2 (3 mL), alpha-toluenesulfonyl chloride (40 mg, 0.21 mmol) and triethylamine (30 μL, 0.21 mmol) are added under N2 atmosphere. The mixture is stirred overnight at RT, diluted with CH2Cl2 and poured into an aqueous saturated solution of NaHCO3. The organic layer is separated, and the aqueous one is extracted twice with CH2Cl2. The combined organic extracts are dried over Na2SO4, filtered and concentrated. The crude product is purified by preparative HPLC (C18-ODB-AQ, 5 μm, 20×50 mm, YMC, eluent: CH3CN /H2O+0.1% HCOOH flow: 20 mL/min). The HPLC fractions are collected, and the resulting solution is lyophilized to afford the title product. TLC, Rf (CH2Cl2/MeOH 95:5)=0.3. tR (HPLC, 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): 5.81 min.

Workup

  1. customThe organic layer is separated
  2. extractionthe aqueous one is extracted twice with CH2Cl2
  3. dry with materialThe combined organic extracts are dried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe crude product is purified by preparative HPLC (C18-ODB-AQ, 5 μm, 20×50 mm, YMC, eluent: CH3CN /H2O+0.1% HCOOH flow: 20 mL/min)
  7. customThe HPLC fractions are collected

Sources & evidence

ORD record
ord-7f1261c2608f4fdc915795ccd3d2e524
Source dataset
uspto-grants-2010_10
Patent number
US07807709B2

Reaction notes

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