(12S,15R)-benzyl 12-(tert-butoxycarbonylamino)-8-(2-(tert-butoxycarbonylamino)ethyl)-2,2-dimethyl-4,9,13-trioxo-15-(4-(trifluoromethyl)benzyl)-3-oxa-5,8,14-triazahexadecan-16-oate → (12S,15R)-12-(tert-butoxycarbonylamino)-8-(2-(tert-butoxycarbonylamino)ethyl)-2,2-dimethyl-4,9,13-trioxo-15-(4-(trifluoromethyl)benzyl)-3-oxa-5,8,14-triazahexadecan-16-oic acid

HRID 1425947Notes

Reaction equation

HRID 1425947 reaction equation
[C:1]([O:5][C:6]([NH:8][C@H:9]([C:35](=[O:59])[NH:36][C@H:37]([CH2:48][C:49]1[CH:54]=[CH:53][C:52]([C:55]([F:58])([F:57])[F:56])=[CH:51][CH:50]=1)[C:38]([O:40]CC1C=CC=CC=1)=[O:39])[CH2:10][CH2:11][C:12](=[O:34])[N:13]([CH2:24][CH2:25][NH:26][C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])[CH2:14][CH2:15][NH:16][C:17](=[O:23])[O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:7])([CH3:4])([CH3:3])[CH3:2]>CCO.O.[Pd]>[C:1]([O:5][C:6]([NH:8][C@H:9]([C:35](=[O:59])[NH:36][C@H:37]([CH2:48][C:49]1[CH:54]=[CH:53][C:52]([C:55]([F:57])([F:58])[F:56])=[CH:51][CH:50]=1)[C:38]([OH:40])=[O:39])[CH2:10][CH2:11][C:12](=[O:34])[N:13]([CH2:24][CH2:25][NH:26][C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])[CH2:14][CH2:15][NH:16][C:17](=[O:23])[O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:7])([CH3:2])([CH3:3])[CH3:4]

Participants

4

Reactant 1

HCID 86702806(12S,15R)-benzyl 12-(tert-butoxycarbonylamino)-8-(2-(tert-butoxycarbonylamino)ethyl)-2,2-dimethyl-4,9,13-trioxo-15-(4-(trifluoromethyl)benzyl)-3-oxa-5,8,14-triazahexadecan-16-oate

Product 1

HCID 68281337(12S,15R)-12-(tert-butoxycarbonylamino)-8-(2-(tert-butoxycarbonylamino)ethyl)-2,2-dimethyl-4,9,13-trioxo-15-(4-(trifluoromethyl)benzyl)-3-oxa-5,8,14-triazahexadecan-16-oic acidYield 99.4%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 19096565Water ethanolSolvent

Procedure

To a solution of (12S,15R)-benzyl 12-(tert-butoxycarbonylamino)-8-(2-(tert-butoxycarbonylamino)ethyl)-2,2-dimethyl-4,9,13-trioxo-15-(4-(trifluoromethyl)benzyl)-3-oxa-5,8,14-triazahexadecan-16-oate (3 g, 3.58 mmol) in a mixture of EtOH/H2O (18 mL/2 mL) was added palladium (wet) on carbon (catalytic amount). The reaction mixture was stirred under an atmosphere of hydrogen at room temperature overnight. The catalyst was filtered through a pad of Celite. The filtrate was evaporated under reduced pressure to give (12S,15R)-12-(tert-butoxycarbonylamino)-8-(2-(tert-butoxycarbonylamino)ethyl)-2,2-dimethyl-4,9,13-trioxo-15-(4-(trifluoromethyl)benzyl)-3-oxa-5,8,14-triazahexadecan-16-oic acid (CLXVI) as white crystals (2.66 g, 3.56 mmol, 99% yield). 1H NMR (DMSO-d6) δ ppm 1.32 (s, 27H), 1.52-1.78 (m, 2H), 2.07-2.26 (m, 2H), 2.9-3.03 (m, 4H), 3.14-3.23 (m, 4H), 3.31 (brs, 2H), 3.83-3.92 (m, 1H), 4.4-4.46 (m, 1H), 6.74-6.85 (m, 2H), 6.88-6.94 (m, 1H), 7.38 (d, J=8 Hz, 2H), 7.55 (d, J=8 Hz, 2H), 7.94-8.01 (m, 1H); 19F NMR (DMSO-d6) δ ppm −60.24 (s, 3F); ESIMS found for C34H52F3N5O10 m/z 748.9 (M+H).

Workup

  1. filtrationThe catalyst was filtered through a pad of Celite
  2. customThe filtrate was evaporated under reduced pressure

Sources & evidence

ORD record
ord-884c673ca6b74c4988dfd22ae712dca0
Source dataset
uspto-grants-2015_01
Patent number
US08933018B2

Reaction notes

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