1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → t-Butyl 3-(Cbz-Val-amido)-5-fluoro-4-liydroxy-pentanoate

HRID 634620Notes

Reaction equation

HRID 634620 reaction equation
[C:1]([NH:11][C@H:12]([C:16]([OH:18])=O)[CH:13]([CH3:15])[CH3:14])([O:3][CH2:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1)=[O:2].CN(C)CCCN=C=NCC.O.ON1C2C=CC=CC=2N=N1.CN(C1C=CC=CN=1)C.[NH2:50][CH:51]([CH:60]([OH:63])[CH2:61][F:62])[CH2:52][C:53]([O:55][C:56]([CH3:59])([CH3:58])[CH3:57])=[O:54]>C1COCC1>[C:1]([NH:11][C@H:12]([C:16]([NH:50][CH:51]([CH:60]([OH:63])[CH2:61][F:62])[CH2:52][C:53]([O:55][C:56]([CH3:57])([CH3:58])[CH3:59])=[O:54])=[O:18])[CH:13]([CH3:14])[CH3:15])([O:3][CH2:4][C:5]1[CH:6]=[CH:7][CH:8]=[CH:9][CH:10]=1)=[O:2]

Participants

7

Reactant 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 218852-DimethylaminopyridineHCID 726987N-Carbobenzoxy-L-valineHCID 27960291-Hydroxybenzotriazole hydrateHCID 108566723-Amino-5-fluoro-4-hydroxy-pentanoic acid tert-butyl ester

Product 1

HCID 21137005t-Butyl 3-(Cbz-Val-amido)-5-fluoro-4-liydroxy-pentanoateYield 68%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of Cbz-Valine (396 mg, 1.58 mmol) in THF (20 mL) was added 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide (EDCI) (300 mg, 1.57 mmol), 1-hydroxybenzotriazole hydrate (HOBT) (240 mg, 1.57 mmol) and dimethylaminopyridine (DMAP) 129 mg 1.06 mmol). The resulting mixture was stirred for 5 min, then was added a solution of t-butyl 3-amino-5-fluoro-4-hydroxy-pentanoate (215 mg, 1.04 mmol) in THF (10 mL) and it was stirred at rt for 18 h. The mixture was filtered and the THF solution was evaporated, and the residue was purified by chromatography over silica gel (hexane-EtOAc, 3:2) to give 290 mg (68%) of the titled compound as a white solid. 1HNMR (CDCl3), 0.905 (d, 3H, J=7), 0.965 (d, 3H, J=7), 1.428 (s, 9H), 2.07-2.16 (m, 1H), 2.50-2.57 (m, 1H), 2.64-2.70 (m, 1H), 3.52 (bs, 1H, OH), 3.92-3.96 (m, 2H), 4.20-4.27 (m, 1H), 4.40 (bs, 1H), 4.49 (bs, 1H), 5.10 (s, 2H), 5.31-5.4 (m, 1H, NH), 6.86-6.93 (m, 1H, NH), 7.350(s, 5H).

Workup

  1. stirringwas stirred at rt for 18 h
  2. filtrationThe mixture was filtered
  3. customthe THF solution was evaporated
  4. customthe residue was purified by chromatography over silica gel (hexane-EtOAc, 3:2)

Sources & evidence

ORD record
ord-0a99772536e74980ad088ca28dd8a20e
Source dataset
uspto-grants-2001_02
Patent number
US06184210B2

Reaction notes

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