Toluene → (S)-Methyl 3-methyl-2-(N-((2'-(1-trityl-1H-tetrazol-5-yl)-[1,1'-biphenyl]-4-yl)methyl)pentanamido)butanoate

HRID 1362770Notes

Reaction equation

HRID 1362770 reaction equation
[C:1]([OH:6])(=O)[C:2](O)=O.[CH3:7][O:8][C:9](=[O:52])[C@H:10]([CH:49]([CH3:51])[CH3:50])[NH:11][CH2:12][C:13]1[CH:18]=[CH:17][C:16]([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=2[C:25]2[N:29]([C:30]([C:43]3[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=3)([C:37]3[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=3)[C:31]3[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=3)[N:28]=[N:27][N:26]=2)=[CH:15][CH:14]=1.[C:53]1(C)[CH:58]=CC=C[CH:54]=1.C(=O)(O)[O-].[Na+]>O>[CH3:7][O:8][C:9](=[O:52])[C@H:10]([CH:49]([CH3:50])[CH3:51])[N:11]([CH2:12][C:13]1[CH:14]=[CH:15][C:16]([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=2[C:25]2[N:29]([C:30]([C:43]3[CH:44]=[CH:45][CH:46]=[CH:47][CH:48]=3)([C:37]3[CH:38]=[CH:39][CH:40]=[CH:41][CH:42]=3)[C:31]3[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=3)[N:28]=[N:27][N:26]=2)=[CH:17][CH:18]=1)[C:1](=[O:6])[CH2:2][CH2:54][CH2:53][CH3:58]

Participants

5

Reactant 3

HCID 1140TolueneHCID 516892Sodium BicarbonateHCID 23725720N-[[2'-(1-triphenylmethyltetrazol-5-yl)biphenyl-4-yl]methyl]valine methyl ester oxalate

Product 1

HCID 16726602(S)-Methyl 3-methyl-2-(N-((2'-(1-trityl-1H-tetrazol-5-yl)-[1,1'-biphenyl]-4-yl)methyl)pentanamido)butanoate

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
7.5 °C

Procedure

N-[[2′-(1-Triphenylmethyltetrazol-5-yl)biphenyl-4-yl]methyl]-L-valine methyl ester oxalate (150 g, 0.215 mole) was added to the mixture of toluene (450 ml) and DM water (300 ml), and basified with 10% w/w aqueous sodium bicarbonate solution (450 ml) at 20-30° C. The organic layer was separated and washed successively with DM water (150 ml) followed by saturated aqueous sodium chloride solution. The organic layer was dried over anhydrous sodium sulfate and reacted with valeryl chloride (33.7 g) in the presence of N,N-Diisopropylethylamine (55.6 g) at 0-5° C. The reaction mixture was stirred for 3 h at 5-10° C. and washed with DM water (150 ml), 10% w/w sodium carbonate solution (68 ml) followed by 10% w/w aqueous oxalic acid solution (40 ml). The organic phase was concentrated completely under reduced pressure to dryness to yield N-[[2′-(1-triphenylmethyltetrazol-5-yl]biphenyl-4-yl]methyl]-N-valeryl-L-valine methyl ester as oily mass (141.3 g)

Workup

  1. customThe organic layer was separated
  2. washwashed successively with DM water (150 ml)
  3. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  4. customreacted with valeryl chloride (33.7 g) in the presence of N,N-Diisopropylethylamine (55.6 g) at 0-5° C
  5. washwashed with DM water (150 ml), 10% w/w sodium carbonate solution (68 ml)
  6. concentrationThe organic phase was concentrated completely under reduced pressure to dryness

Sources & evidence

ORD record
ord-8349bf78e31540c1a6a7bcd18084dc21
Source dataset
uspto-grants-2011_02
Patent number
US07880015B2

Reaction notes

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