Tetrahydrofuran → Fmoc-Phe-Lys(Mtr)

HRID 1883295Notes

Reaction equation

HRID 1883295 reaction equation
[NH2:1][C@H:2]([C:22]([OH:24])=[O:23])[CH2:3][CH2:4][CH2:5][CH2:6][NH:7][S:8]([C:11]1[C:20]([CH3:21])=[C:18]([CH3:19])[C:15]([O:16][CH3:17])=[CH:14][C:12]=1[CH3:13])(=[O:10])=[O:9].C([O-])(O)=O.[Na+].[NH:30]([C:49]([O:51][CH2:52][CH:53]1[C:65]2[C:60](=[CH:61][CH:62]=[CH:63][CH:64]=2)[C:59]2[C:54]1=[CH:55][CH:56]=[CH:57][CH:58]=2)=[O:50])[C@H:31]([C:39](ON1C(=O)CCC1=O)=[O:40])[CH2:32][C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1.C1COCC1>O.COCCOC>[NH:30]([C:49]([O:51][CH2:52][CH:53]1[C:65]2[C:60](=[CH:61][CH:62]=[CH:63][CH:64]=2)[C:59]2[C:54]1=[CH:55][CH:56]=[CH:57][CH:58]=2)=[O:50])[C@H:31]([C:39]([NH:1][C@H:2]([C:22]([OH:24])=[O:23])[CH2:3][CH2:4][CH2:5][CH2:6][NH:7][S:8]([C:11]1[C:20]([CH3:21])=[C:18]([CH3:19])[C:15]([O:16][CH3:17])=[CH:14][C:12]=1[CH3:13])(=[O:10])=[O:9])=[O:40])[CH2:32][C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1

Participants

7

Reactant 4

HCID 8028TetrahydrofuranHCID 516892Sodium BicarbonateHCID 11826988Fmoc-Phe-OSuHCID 15662507Lys(Mtr)

Product 1

HCID 131724481Fmoc-Phe-Lys(Mtr)

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolvent2×

Procedure

A suspension of Lys(Mtr) 2 (4.686 g, 11.20 mmol) and NaHCO3 (941.0 mg, 1 equiv) in water (100 mL) and DME (50 mL) was treated with a solution of Fmoc-Phe-OSu 7a (11.20 mmol) in DME (50 mL). THF (25 mL) was then added to aid solubility. The mixture was stirred at rt for 2 days and then as much DME as possible was removed on the rotovap (bath at 30° C.). The resulting gummy suspension was partitioned between ethyl acetate and pH 5 buffer. The organic phase was washed with water and brine, dried and evaporated to give a pale yellow foam. This was flushed with methylene chloride (100 mL). TLC showed the product to be satisfactorily pure and it was carried on without further purification (8.559 g, 97%). 1H-NMR (CDCl3/CD3OD) δ 1.10-1.93 (m, 6H), 2.31 (t, 2H), 3.00 (m, 2H), 3.71 (s, 3H), 4.02-4.48 (m, 5H), 6.79 (d, 2H), 7.00-7.75 (m, 25H). MS (FAB) 788.2 (MH)+, 810.4 (M+Na)+, 826 (M+K)+. Anal. Calcd for C50H49N3O6—H2O: C-74.51, H-6.38, N-5.21. Found: C-74.17, H-6.57, N-5.41.

Workup

  1. customas much DME as possible was removed on the rotovap (bath at 30° C.)
  2. customThe resulting gummy suspension was partitioned between ethyl acetate and pH 5 buffer
  3. washThe organic phase was washed with water and brine
  4. customdried
  5. customevaporated
  6. customto give a pale yellow foam
  7. customThis was flushed with methylene chloride (100 mL)
  8. customit was carried on without further purification (8.559 g, 97%)

Sources & evidence

ORD record
ord-4f8d6d562d3046d693c7842fbebd5001
Source dataset
uspto-grants-2004_07
Patent number
US06759509B1

Reaction notes

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