Tributylamine → (S)-4-Benzyloxy-2-[[2-(3,4-dichloro-phenylamino)-propyl]-(3,3-dimethoxy-propionyl)-amino]-butyric Acid methyl ester

HRID 1096265Notes

Reaction equation

HRID 1096265 reaction equation
[CH3:1][O:2][C:3](=[O:28])[C@@H:4]([NH:15][CH2:16][CH:17]([NH:19][C:20]1[CH:25]=[CH:24][C:23]([Cl:26])=[C:22]([Cl:27])[CH:21]=1)[CH3:18])[CH2:5][CH2:6][O:7][CH2:8][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1.[I-].ClC1C=CC=C[N+]=1C.[CH3:38][O:39][CH:40]([O:45][CH3:46])[CH2:41][C:42](O)=[O:43].C(N(CCCC)CCCC)CCC>C(Cl)Cl>[CH3:1][O:2][C:3](=[O:28])[C@@H:4]([N:15]([CH2:16][CH:17]([NH:19][C:20]1[CH:25]=[CH:24][C:23]([Cl:26])=[C:22]([Cl:27])[CH:21]=1)[CH3:18])[C:42](=[O:43])[CH2:41][CH:40]([O:45][CH3:46])[O:39][CH3:38])[CH2:5][CH2:6][O:7][CH2:8][C:9]1[CH:10]=[CH:11][CH:12]=[CH:13][CH:14]=1

Participants

6

Reactant 4

HCID 7622TributylamineHCID 1670692-Chloro-1-methylpyridinium iodideHCID 103745043,3-dimethoxypropanoic AcidHCID 66783303(S)-4-Benzyloxy-2-[2-(3,4-dichloro-phenylamino)-propylamino]-butyric acid methyl ester

Product 1

HCID 66782917(S)-4-Benzyloxy-2-[[2-(3,4-dichloro-phenylamino)-propyl]-(3,3-dimethoxy-propionyl)-amino]-butyric Acid methyl esterYield 96%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

A solution of 1.26 g (2.96 mmol) of (S)-4-benzyloxy-2-[2-(3,4-dichloro-phenylamino)-propylamino]-butyric acid methyl ester in 30 ml CH2Cl2 was treated with a solution of 0.91 g (3.55 mmol) of 2-chloro-1-methylpyridinium iodide and 0.48 g (3.55 mmol) of 3,3-dimethoxy-propionic acid (synthesized from methyl 3,3-dimethoxy-propionate by hydrolysis with LiOH) in 20 ml of CH2Cl2. The suspension was cooled and treated at 0° C. with 1.77 ml (7.41 mmol) of tributylamine. The cooling bath was removed after 10 min and stirring was continued over night. The reaction was extracted with 10% aq. KHSO4 solution/diethyl ether (3×). The organic phases were washed with 10% aq. KHSO4 solution (2×), sat. aq. NaHCO3 solution, 10% aq. NaCl solution and dried over Na2SO4 to yield 1.53 g (96%) of the title compound as a 71:29 mixture of the (R) and (S) diastereomers. Yellow oil, MS: 541.2 (MH+, 2Cl).

Workup

  1. temperatureThe suspension was cooled
  2. customThe cooling bath was removed after 10 min
  3. waitwas continued over night
  4. extractionThe reaction was extracted with 10% aq. KHSO4 solution/diethyl ether (3×)
  5. washThe organic phases were washed with 10% aq. KHSO4 solution (2×), sat. aq. NaHCO3 solution, 10% aq. NaCl solution
  6. dry with materialdried over Na2SO4

Sources & evidence

ORD record
ord-0980f5cec6014ec08891d795bda52bf3
Source dataset
uspto-grants-2012_03
Patent number
US08138175B2

Reaction notes

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