Iodoethane → (3S,4S)-3-[(5-chloro-thiophene-2-carbonyl)-amino]-4-ethoxy-pyrrolidine-1-carboxylic acid tert-butyl ester

HRID 1162639Notes

Reaction equation

HRID 1162639 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:12][C@H:11]([OH:13])[C@@H:10]([NH:14][C:15]([C:17]2[S:18][C:19]([Cl:22])=[CH:20][CH:21]=2)=[O:16])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].I[CH2:24][CH3:25]>CC#N.C1COCC1.[Ag-]=O>[C:1]([O:5][C:6]([N:8]1[CH2:12][C@H:11]([O:13][CH2:24][CH3:25])[C@@H:10]([NH:14][C:15]([C:17]2[S:18][C:19]([Cl:22])=[CH:20][CH:21]=2)=[O:16])[CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 2

HCID 6340Iodoethane2×HCID 42643219(3S,4S)-3-[(5-chloro-thiophene-2-carbonyl)-amino]-4-hydroxy-pyrrolidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 42643220(3S,4S)-3-[(5-chloro-thiophene-2-carbonyl)-amino]-4-ethoxy-pyrrolidine-1-carboxylic acid tert-butyl ester

Reagents, catalysts & solvents 3

HCID 178418778HCID 178418778, compoundCatalyst2×HCID 6342AcetonitrileSolventHCID 8028TetrahydrofuranSolvent

Procedure

29.1 A solution of 150 mg (3S,4S)-3-[(5-chloro-thiophene-2-carbonyl)-amino]-4-hydroxy-pyrrolidine-1-carboxylic acid tert-butyl ester (example 22.4) in 3 ml MeCN and 1 ml THF was treated with 300 mg silver(I) oxide and 0.35 ml iodoethane. The reaction mixture was stirred over night, then was again treated with 300 mg silver(I) oxide and 0.35 ml iodoethane. The reaction mixture was agitated over night at r.t., then filtrated. The filtrate was concentrated. The crude product was purified by chromatography (silica gel; gradient: cyclohexane->EtOAc) to give 90 mg (3S,4S)-3-[(5-chloro-thiophene-2-carbonyl)-amino]-4-ethoxy-pyrrolidine-1-carboxylic acid tert-butyl ester as light yellow oil. MS 373.1 ([M−H]−)

Workup

  1. stirringThe reaction mixture was agitated over night at r.t.
  2. filtrationfiltrated
  3. concentrationThe filtrate was concentrated
  4. customThe crude product was purified by chromatography (silica gel; gradient: cyclohexane->EtOAc)

Sources & evidence

ORD record
ord-518983285829480dbe8e8c2129e46a09
Source dataset
uspto-grants-2010_10
Patent number
US07820699B2

Reaction notes

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