(S)-2-((S)-2-tert-butoxycarbonylamino-3-difluoromethoxy-propionylamino)-3-di-fluoromethoxy-propionic acid benzyl ester → (S)-2-((S)-2-tert-butoxycarbonylamino-3-difluoromethoxy-propionylamino)-3-difluoromethoxy-propionic acid

HRID 61293Notes

Reaction equation

HRID 61293 reaction equation
C([O:8][C:9](=[O:33])[C@@H:10]([NH:16][C:17](=[O:32])[C@@H:18]([NH:24][C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])[CH2:19][O:20][CH:21]([F:23])[F:22])[CH2:11][O:12][CH:13]([F:15])[F:14])C1C=CC=CC=1>C1COCC1.[Pd]>[C:28]([O:27][C:25]([NH:24][C@@H:18]([CH2:19][O:20][CH:21]([F:22])[F:23])[C:17]([NH:16][C@@H:10]([CH2:11][O:12][CH:13]([F:15])[F:14])[C:9]([OH:33])=[O:8])=[O:32])=[O:26])([CH3:31])([CH3:29])[CH3:30]

Participants

4

Reactant 1

HCID 90040250(S)-2-((S)-2-tert-butoxycarbonylamino-3-difluoromethoxy-propionylamino)-3-di-fluoromethoxy-propionic acid benzyl ester

Product 1

HCID 90040906(S)-2-((S)-2-tert-butoxycarbonylamino-3-difluoromethoxy-propionylamino)-3-difluoromethoxy-propionic acidYield 100%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 8028TetrahydrofuranSolvent

Procedure

A solution of the compound of Formula II(a)(ii), (S)-2-((S)-2-tert-butoxycarbonylamino-3-difluoromethoxy-propionylamino)-3-difluoromethoxypropionic acid benzyl ester (1.27 g, 2.63 mmol) in THF was stirred with 10% Pd/C (400 mg) under a hydrogen atmosphere for 1 hour. The reaction mixture was filtered and concentrated to give the compound of Formula II(a)(i), (S)-2-((S)-2-tert-butoxycarbonylamino-3-difluoromethoxy-propionylamino)-3-difluoromethoxy-propionic acid (1.03 g, ˜100%) as a sticky, off-white foam. NMR (d6-DMSO, 400 MHz) δ (ppm) 8.34 (d, J=8 Hz, 1H), 7.12 (d, J=8 Hz, 1H), 6.66 (t, J=76 Hz, 1H), 6.62 (t, J=76 Hz, 1H), 4.57-4.51 (m, 1H), 4.37-4.29 (m, 1H), 4.15-4.09 (m, 1H), 4.04-3.97 (m, 2H), 3.92-3.83 (m, 1H), 1.37 (s, 9H). Scheme VII outlines the synthesis of compound intermediates of Formula IV(b) and Formula V(b) which are used in the preparation of the compounds of Formula (I) wherein R2 and/or R3 is a —CH2—O—CH3 moiety.

Workup

  1. filtrationThe reaction mixture was filtered
  2. concentrationconcentrated

Sources & evidence

ORD record
ord-b7ddc2f6442c4a32aa4db182aac85daf
Source dataset
uspto-grants-2016_09
Patent number
US09441012B2

Reaction notes

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