Thiophenol → tert-butyl (2R,5S)-2-[2-(2-{[N-(methoxycarbonyl)-beta-phenyl-L-phenylalanyl]amino}phenyl)ethyl]-5-[(phenylsulfanyl)methyl]morpholine-4-carboxylate

HRID 629719Notes

Reaction equation

HRID 629719 reaction equation
C(C=P(CCCC)(CCCC)CCCC)#N.[C:17]([O:21][C:22]([N:24]1[C@H:29]([CH2:30]O)[CH2:28][O:27][C@H:26]([CH2:32][CH2:33][C:34]2[CH:39]=[CH:38][CH:37]=[CH:36][C:35]=2[NH:40][C:41](=[O:61])[C@@H:42]([NH:56][C:57]([O:59][CH3:60])=[O:58])[CH:43]([C:50]2[CH:55]=[CH:54][CH:53]=[CH:52][CH:51]=2)[C:44]2[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=2)[CH2:25]1)=[O:23])([CH3:20])([CH3:19])[CH3:18].[C:62]1([SH:68])[CH:67]=[CH:66][CH:65]=[CH:64][CH:63]=1>C1(C)C=CC=CC=1>[CH3:60][O:59][C:57]([NH:56][C@H:42]([C:41]([NH:40][C:35]1[CH:36]=[CH:37][CH:38]=[CH:39][C:34]=1[CH2:33][CH2:32][C@H:26]1[O:27][CH2:28][C@@H:29]([CH2:30][S:68][C:62]2[CH:67]=[CH:66][CH:65]=[CH:64][CH:63]=2)[N:24]([C:22]([O:21][C:17]([CH3:20])([CH3:18])[CH3:19])=[O:23])[CH2:25]1)=[O:61])[CH:43]([C:50]1[CH:51]=[CH:52][CH:53]=[CH:54][CH:55]=1)[C:44]1[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=1)=[O:58]

Participants

5

Reactant 3

HCID 7969ThiophenolHCID 4622928CyanomethylenetributylphosphoraneHCID 86726307(2R,5R)-5-hydroxymethyl-2-{2-[2-((S)-2-methoxycarbonylamino-3,3-diphenyl-propionylamino)-phenyl]-ethyl}-morpholine-4-carboxylic acid tert-butyl ester

Product 1

HCID 86726322tert-butyl (2R,5S)-2-[2-(2-{[N-(methoxycarbonyl)-beta-phenyl-L-phenylalanyl]amino}phenyl)ethyl]-5-[(phenylsulfanyl)methyl]morpholine-4-carboxylate

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
90 °C

Procedure

Cyanomethylenetributylphosphorane (2 eq) was added to a stirred mixture of (2R,5R)-5-hydroxymethyl-2-{2-[2-((S)-2-methoxycarbonylamino-3,3-diphenyl-propionylamino)-phenyl]-ethyl}-morpholine-4-carboxylic acid tert-butyl ester (1 eq) and thiophenol (1.5 eq) in toluene (0.04 M). The mixture was stirred at 90° C. for 2 h, cooled to room temperature and evaporated to dryness. The residue was purified by automated silica gel flash chromatography system eluted with a gradient 0% to 100% of EtOAc/Hex to afford tert-butyl (2R,5S)-2-[2-(2-{[N-(methoxycarbonyl)-β-phenyl-L-phenylalanyl]amino}phenyl)ethyl]-5-[(phenylsulfanyl)methyl]morpholine-4-carboxylate which was then treated with TFA following the procedure described in step 2 of Example 2 to afford the title compound.

Workup

  1. temperaturecooled to room temperature
  2. customevaporated to dryness
  3. customThe residue was purified by automated silica gel flash chromatography system
  4. washeluted with a gradient 0% to 100% of EtOAc/Hex

Sources & evidence

ORD record
ord-055d14afd2a449f89388cf12ca0ac0e7
Source dataset
uspto-grants-2016_04
Patent number
US09315475B2

Reaction notes

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