tert-Butanol → 1-Benzyloxycarbonyl-4-(R)-(1-tert-butoxycarbonylaminocyclopropyl)-3-(R)-methoxypyrrolidine

HRID 635076Notes

Reaction equation

HRID 635076 reaction equation
[CH2:1]([O:8][C:9]([N:11]1[CH2:15][C@H:14]([O:16][CH3:17])[C@@H:13]([C:18]2(C(O)=O)[CH2:20][CH2:19]2)[CH2:12]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C1(P(N=[N+]=[N-])(C2C=CC=CC=2)=[O:31])C=CC=CC=1.C([N:43]([CH2:46]C)CC)C.[C:48]([OH:52])([CH3:51])([CH3:50])[CH3:49]>>[CH2:1]([O:8][C:9]([N:11]1[CH2:12][C@H:13]([C:18]2([NH:43][C:46]([O:52][C:48]([CH3:51])([CH3:50])[CH3:49])=[O:31])[CH2:19][CH2:20]2)[C@@H:14]([O:16][CH3:17])[CH2:15]1)=[O:10])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 4

HCID 6386tert-ButanolHCID 8471TriethylamineHCID 199401P,P-Diphenylphosphinic azideHCID 542347281-[1-Benzyloxycarbonyl-4-(R)-methoxy-3-(S)-pyrrolidinyl]cyclopropanecarboxylic acid

Product 1

HCID 219712631-Benzyloxycarbonyl-4-(R)-(1-tert-butoxycarbonylaminocyclopropyl)-3-(R)-methoxypyrrolidineYield 50%

Procedure

1-[1-Benzyloxycarbonyl-4-(R)-methoxy-3-(S)-pyrrolidinyl]cyclopropanecarboxylic acid (713 mg, 2.22 mmol) was dissolved in tert-butyl alcohol (20 ml), and the solution was mixed with diphenylphosphoryl azide (623 μl, 2.89 mmol) and triethylamine (775 μl, 5.56 mmol), stirred at room temperature for 20 minutes and then heated under reflux for 19 hours. The reaction solution was cooled and then concentrated under reduced pressure, and the resulting residue was subjected to flash silica gel chromatography and eluted with an eluant of n-hexane:ethyl acetate=3:2, to thereby obtain the title compound (431 mg, 50%) as a colorless oil.

Workup

  1. temperatureheated
  2. temperatureunder reflux for 19 hours
  3. temperatureThe reaction solution was cooled
  4. concentrationconcentrated under reduced pressure
  5. washeluted with an eluant of n-hexane

Sources & evidence

ORD record
ord-64fa3429436f4391a76428d487d8ae0a
Source dataset
uspto-grants-2001_02
Patent number
US06184388B2

Reaction notes

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