Imidazole → N-Boc-5-Iodo-D-norvaline tert-butyl ester

HRID 651316Notes

Reaction equation

HRID 651316 reaction equation
[C:1]([O:5][C:6](=[O:20])[C@H:7]([NH:12][C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[CH2:8][CH2:9][CH2:10]O)([CH3:4])([CH3:3])[CH3:2].N1C=CN=C1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[I:45]I>C1COCC1>[C:1]([O:5][C:6](=[O:20])[C@H:7]([NH:12][C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[CH2:8][CH2:9][CH2:10][I:45])([CH3:4])([CH3:3])[CH3:2]

Participants

6

Reactant 4

HCID 795ImidazoleHCID 807IodineHCID 11776TriphenylphosphineHCID 15814357tert-butyl (2R)-2-{[(tert-butoxy)carbonyl]amino}-5-hydroxypentanoate

Product 1

HCID 15479355N-Boc-5-Iodo-D-norvaline tert-butyl esterYield 72%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of the title E compound, (2R)-(t-butyloxycarbonylamino)-5-hydroxypentanoic acid t-butyl ester (9.12 g, 31.5 mmol), imidazole (3.22 g, 47.3 mmol) and triphenylphosphine (12.40 g, 47.3 mmol) in 300 mL of THF is treated portionwise over 5 min with iodine (9.60 g, 37.8 mmol) at RT. After 2 h, the mixture is filtered and concentrated. The residue is first filtrated though silica gel (eluant; ethyl acetate) then purified by chomatography on silica gel (eluant; 10% ethyl acetate in hexane) affording 9.05 g (72%) of (2R)-(t-butyloxycarbonylamino)-5-iodopentanoic acid t-butyl ester as a colorless oil: NMR(CDCl3)) 1.42 (s, 9H), 1.46 (s, 9H), 1.65-1.95 (m, 4H), 3.14-3.28 (m, 2H), 4.19-4.26 (m, 1H), 5.06 (br d, 1H, J=7.4); IR 1712, 1500, 1155; ESI-MS 400 (M++1).

Workup

  1. filtrationthe mixture is filtered
  2. concentrationconcentrated
  3. filtrationThe residue is first filtrated though silica gel (eluant; ethyl acetate)
  4. customthen purified by chomatography on silica gel (eluant; 10% ethyl acetate in hexane)

Sources & evidence

ORD record
ord-466ade5bfc7544c2befb976ad626df1b
Source dataset
uspto-grants-2001_08
Patent number
US06277987B1

Reaction notes

Loading…