Water → HCID 86642472, compound

HRID 1923985Notes

Reaction equation

HRID 1923985 reaction equation
[CH2:1]([O:8][C:9]([NH:11][C@H:12]([CH2:16][S:17][S:18][CH2:19][C@@H:20]([NH:24][C:25]([O:27][CH2:28][C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1)=[O:26])[C:21]([OH:23])=[O:22])[C:13]([OH:15])=[O:14])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(=O)([O-])[O-].[K+].[K+].[CH2:41](Br)[C:42]1[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=1.O>CN(C=O)C>[CH2:41]([O:14][C:13](=[O:15])[C@H:12]([NH:11][C:9]([O:8][CH2:1][C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1)=[O:10])[CH2:16][S:17][S:18][CH2:19][C@@H:20]([NH:24][C:25]([O:27][CH2:28][C:29]1[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=1)=[O:26])[C:21]([O:23][CH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1)=[O:22])[C:42]1[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=1

Participants

6

Reactant 4

HCID 962WaterHCID 7498Benzyl BromideHCID 11430Potassium CarbonateHCID 7163266HCID 7163266, compound

Product 1

HCID 86642472HCID 86642472, compoundYield 77.8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of (2S)-2-{[(benzyloxy)carbonyl]amino}-3-{[(2S)-2-{[(benzyloxy)carbonyl]amino}-2-carboxyethyl]disulfanyl}propanoic acid LXVI (5.6 g; 11 mmol) and anhydrous potassium carbonate (6.08 g; 44.0 mmol) in DMF (50 mL) cooled to 0° C. was added benzyl bromide (7.8 mL; 66.0 mmol). The mixture was stirred overnight at r.t. Water (150 mL) was added, and solution was extracted once with DCM (40 mL). The solvent was evaporated under reduced pressure and the residue was dissolved in diethyl ether (60 mL). The ether was washed with 10% aq Na2S2O3 until all the DMF was removed and once with water. The organic phase was dried over anhydrous MgSO4, evaporated and the residue purified on a silica gel column (100% CHCl3→200:3 CHCl3:MeOH). Benzyl (2S)-3-{[(2S)-3-(benzyloxy)-2-{[(benzyloxy)carbonyl]amino}-3-oxopropyl]disulfanyl}-2-{[(benzyloxy)carbonyl]amino}propanoate LXVII was obtained as a light-green viscous oil (5.9 g; 8.56 mmol; 77.8% yield). 1H NMR (CDCl3) 3.04-3.18 (m, 4H), 4.62-4.76 (m, 2H), 5.12 (s, 2H), 5.17 (s, 2H), 5.62-5.76 (m, 2H), 7.28-7.40 (m, 20H); ESIMS found for C36H36N2O8S2 m/z 689.5 (M+H).

Workup

  1. extractionsolution was extracted once with DCM (40 mL)
  2. customThe solvent was evaporated under reduced pressure
  3. dissolutionthe residue was dissolved in diethyl ether (60 mL)
  4. washThe ether was washed with 10% aq Na2S2O3 until all the DMF
  5. customwas removed and once with water
  6. dry with materialThe organic phase was dried over anhydrous MgSO4
  7. customevaporated
  8. customthe residue purified on a silica gel column (100% CHCl3→200:3 CHCl3:MeOH)

Sources & evidence

ORD record
ord-a8f4a19ee6294ff7b017726551226c1e
Source dataset
uspto-grants-2012_05
Patent number
US08178490B2

Reaction notes

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