Triphenylphosphine → Boc-Ala-Ala-NH-(CH2)4-N(Ns)-Ala-OMe

HRID 1044648Notes

Reaction equation

HRID 1044648 reaction equation
[NH:1]([S:8]([C:11]1[CH:19]=[CH:18][C:14]([N+:15]([O-:17])=[O:16])=[CH:13][CH:12]=1)(=[O:10])=[O:9])[C@H:2]([C:4]([O:6][CH3:7])=[O:5])[CH3:3].[NH:20]([C:36]([O:38][C:39]([CH3:42])([CH3:41])[CH3:40])=[O:37])[C@H:21]([C:23]([NH:25][C@H:26]([C:28]([NH:30][CH2:31][CH2:32][CH2:33][CH2:34]O)=[O:29])[CH3:27])=[O:24])[CH3:22].C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.CC(OC(/N=N/C(OC(C)C)=O)=O)C>C1COCC1.C(Cl)Cl.CO>[NH:20]([C:36]([O:38][C:39]([CH3:42])([CH3:40])[CH3:41])=[O:37])[C@H:21]([C:23]([NH:25][C@H:26]([C:28]([NH:30][CH2:31][CH2:32][CH2:33][CH2:34][N:1]([S:8]([C:11]1[CH:19]=[CH:18][C:14]([N+:15]([O-:17])=[O:16])=[CH:13][CH:12]=1)(=[O:9])=[O:10])[C@H:2]([C:4]([O:6][CH3:7])=[O:5])[CH3:3])=[O:29])[CH3:27])=[O:24])[CH3:22]

Participants

8

Reactant 4

HCID 11776Triphenylphosphine2×HCID 5363146Diisopropyl azodicarboxylate2×HCID 7035709Ns-Ala-OMeHCID 59537080Boc-Ala-Ala-NH-(CH2)4-OH

Product 1

HCID 131730909Boc-Ala-Ala-NH-(CH2)4-N(Ns)-Ala-OMe

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a cold (−15° C.) vigorously stirring solution of Ns-Ala-OMe (50 mg, 0.17 mmol), Boc-Ala-Ala-NH—(CH2)4—OH (57 mg, 0.17 mmol) and PPh3 (68 mg, 0.26 mmol) in dry THF (1.5 mL) was added DIAD (53 mg, 0.26 mmol) slowly dropwise. After 7 h another portion of PPh3 (68 mg, 0.26 mmol) and DIAD (52 mg, 0.26 mmol) was added and stirred for further 10 h, when TLC (MeOH:DCM) indicated complete consumption of the starting material. The mixture was concentrated under vacuum and the resulting residue was diluted with EtOAc (15 mL), washed with water (2 mL), dried over Na2SO4 and concentrated under vacuum to give a crude residue which was purified by silica gel flash column chromatography (EtOAc:Hexanes—3:1) to give the desired product as a viscous oil in good yields (71 mg, 76%). TLC (MeOH:DCM—1:9—Rf=0.5).

Workup

  1. customconsumption of the starting material
  2. concentrationThe mixture was concentrated under vacuum
  3. additionthe resulting residue was diluted with EtOAc (15 mL)
  4. washwashed with water (2 mL)
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated under vacuum
  7. customto give a crude residue which
  8. customwas purified by silica gel flash column chromatography (EtOAc:Hexanes—3:1)

Sources & evidence

ORD record
ord-ebd85dd8d28d4464bdc7c3cf54c1f09f
Source dataset
uspto-grants-2013_10
Patent number
US08563686B2

Reaction notes

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