Tributylphosphine → HCID 178454072, compound
Reaction equation
[C:1]([O:5][C:6](=[O:15])[NH:7][C@H:8]1[CH2:13][CH2:12][C@@H:11]([OH:14])[CH2:10][CH2:9]1)([CH3:4])([CH3:3])[CH3:2].N(C(N1CCCCC1)=O)=NC(N1CCCCC1)=O.C(P(CCCC)CCCC)CCC.[F:47][C:48]([F:57])([C:51]1[CH:56]=[CH:55][CH:54]=[CH:53][CH:52]=1)[CH2:49]O>C1(C)C=CC=CC=1.C1C=CC=CC=1>[C:1]([O:5][C:6](=[O:15])[NH:7][C@H:8]1[CH2:9][CH2:10][C@H:11]([O:14][CH2:49][C:48]([F:57])([F:47])[C:51]2[CH:56]=[CH:55][CH:54]=[CH:53][CH:52]=2)[CH2:12][CH2:13]1)([CH3:4])([CH3:2])[CH3:3]Participants
Conditions
- Temperature
- 60 °C
Procedure
To a stirred mixture of 0.23 g of g of cis-(4-hydroxy-cyclohexyl)-carbamic acid tert-butyl ester, 0.54 g of 1.1′-(azodicarbonyl)-dipiperidine and 20 mL of benzene was added 0.4 g of tri-n-butyl-phosphine and 1.3 g (8 equivalents) of 2,2-difluoro-2-phenyl-ethanol. The mixture was heated to 60° C. overnight, then an additional 0.5 g of 1.1′-(azodicarbonyl)-dipiperidine and 0.4 g of tri-n-butyl-phosphine was added and heating continued for another 24 h. The mixture was cooled, diluted with 25 mL of toluene, filtered and the filter pad washed with 5 mL of toluene. The filtrate was purified by chromatography on silica gel eluting with a gradient of 0%-20% ethyl acetate in hexane gave 0.15 g of product as a resin: 1H NMR (400 MHz, CDCl3) 7.5 (m, 5H), 3.95 (m, 2H), 3.4 (m, 1H), 1.95 (m, 2H), 1.6 (m, 6H), 1.45 (s, 9H).
Workup
- temperatureheating
- temperatureThe mixture was cooled
- filtrationfiltered
- washthe filter pad washed with 5 mL of toluene
- customThe filtrate was purified by chromatography on silica gel eluting with a gradient of 0%-20% ethyl acetate in hexane
Sources & evidence
- ORD record
- ord-e6ed7fbff69c4de0bd60b1cad2f4e5eb
- Source dataset
- uspto-grants-2008_11
- Patent number
- US07452893B2
Reaction notes
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