1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → (2S,4R)-{[1-(Naphthalene-2-sulfonyl)-4-tritylsulfanyl-pyrrolidine-2-carbonyl]-phenethyl-amino]-acetic acid tert-butyl ester

HRID 1264397Notes

Reaction equation

HRID 1264397 reaction equation
[CH:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][C:2]=1[S:11]([N:14]1[CH2:18][C@H:17]([S:19][C:20]([C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=2)([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[CH2:16][C@H:15]1[C:39](O)=[O:40])(=[O:13])=[O:12].[C:42]([O:46][C:47](=[O:58])[CH2:48][NH:49][CH2:50][CH2:51][C:52]1[CH:57]=[CH:56][CH:55]=[CH:54][CH:53]=1)([CH3:45])([CH3:44])[CH3:43].CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1>C1COCC1>[C:42]([O:46][C:47](=[O:58])[CH2:48][N:49]([C:39]([C@@H:15]1[CH2:16][C@@H:17]([S:19][C:20]([C:21]2[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=2)([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[C:33]2[CH:34]=[CH:35][CH:36]=[CH:37][CH:38]=2)[CH2:18][N:14]1[S:11]([C:2]1[CH:1]=[CH:10][C:5]2[C:4](=[CH:9][CH:8]=[CH:7][CH:6]=2)[CH:3]=1)(=[O:12])=[O:13])=[O:40])[CH2:50][CH2:51][C:52]1[CH:53]=[CH:54][CH:55]=[CH:56][CH:57]=1)([CH3:45])([CH3:43])[CH3:44]

Participants

6

Reactant 4

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 14461641Tert-butyl 2-[(2-phenylethyl)amino]acetateHCID 69428772(2S,4R)-1-(Naphthalene-2-sulfonyl)-4-tritylsulfanyl-pyrrolidine-2-carboxylic acid

Product 1

HCID 70001340(2S,4R)-{[1-(Naphthalene-2-sulfonyl)-4-tritylsulfanyl-pyrrolidine-2-carbonyl]-phenethyl-amino]-acetic acid tert-butyl esterYield 26.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of 800 mg (1.38 mmol) (2S,4R)-1-(Naphthalene-2-sulfonyl)-4-tritylsulfanyl-pyrrolidine-2-carboxylic acid and 390 mg (1.66 mmol) crude phenethylamino-acetic acid tert-butyl ester in 14 ml THF was cooled to 0° C. and treated with 318 mg (1.66 mmol) EDCI and 19 mg (0.14 mmol) HOBT. The reaction was warmed up to RT over night and partitioned between aqueous 10% KHSO4/ethyl acetate (3×). The organic phases were washed with aqueous saturated NaHCO3 solution and dried over Na2SO4. Purification by flash-chromatography on silicagel (Hexane/EtOAc 4:1 to 1:1) gave 290 mg (26%) (2S,4R)-{[1-(Naphthalene-2-sulfonyl)-4-tritylsulfanyl-pyrrolidine-2-carbonyl]-phenethyl-amino}-acetic acid tert-butyl ester, MS: 797 (MH+)

Workup

  1. custompartitioned between aqueous 10% KHSO4/ethyl acetate (3×)
  2. washThe organic phases were washed with aqueous saturated NaHCO3 solution
  3. dry with materialdried over Na2SO4
  4. customPurification by flash-chromatography on silicagel (Hexane/EtOAc 4:1 to 1:1)

Sources & evidence

ORD record
ord-8205d4fa74a64b63aa9a846444454dba
Source dataset
uspto-grants-2003_04
Patent number
US06541638B2

Reaction notes

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