4-Methylmorpholine → HCID 131733463, compound

HRID 2278372Notes

Reaction equation

HRID 2278372 reaction equation
[CH3:1][O:2][C:3]([NH:5][C@H:6]([C:20](O)=[O:21])[CH:7]([C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)=[O:4].CN1CCOCC1.ClC(OCC(C)C)=O.[CH2:38]([O:41][C:42](=[O:65])[NH:43][C@@H:44]([C:54]1[S:55][C:56]([C@@H:59]([NH2:64])[C:60]([F:63])([F:62])[F:61])=[CH:57][CH:58]=1)[CH2:45][O:46][Si:47]([C:50]([CH3:53])([CH3:52])[CH3:51])([CH3:49])[CH3:48])[CH:39]=[CH2:40].CCN(C(C)C)C(C)C.C(=O)(O)[O-].[Na+]>ClCCl>[CH2:38]([O:41][C:42](=[O:65])[NH:43][C@@H:44]([C:54]1[S:55][C:56]([C@@H:59]([NH:64][C:20](=[O:21])[C@H:6]([CH:7]([C:8]2[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=2)[C:14]2[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=2)[NH:5][C:3]([O:2][CH3:1])=[O:4])[C:60]([F:61])([F:62])[F:63])=[CH:57][CH:58]=1)[CH2:45][O:46][Si:47]([C:50]([CH3:53])([CH3:52])[CH3:51])([CH3:49])[CH3:48])[CH:39]=[CH2:40]

Participants

8

Reactant 6

HCID 79724-MethylmorpholineHCID 62365Isobutyl chloroformateHCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 10017620(S)-2-methoxycarbonylamino-3,3-diphenyl-propionic acidHCID 131733462HCID 131733462, compound

Product 1

HCID 131733463HCID 131733463, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of N-(methoxycarbonyl)-β-phenyl-L-phenylalanine (3.2 g, 10.6 mmol) in dichloromethane (70 mL) was cooled to −15° C., and then was added N-methylmorpholine (1.17 mL, 10.6 mmol) and isobutyl chloroformate and the mixture was stirred for 30 minutes. A solution of prop-2-en-1-yl[(1R)-1-{5-[(1S)-1-amino-2,2,2-trifluoroethyl]thiophen-2-yl}-2-{[tert-butyl(dimethyl)silyl]oxy}ethyl]carbamate (3.1 g, 7.07 mmol) and Hunig's base (1.48 mL, 8.48 mmol) in dichloromethane (70 mL) cooled to −15° C. was added to the mixed anhydride solution. The mixture was allowed to warm up to room temperature by stirring overnight. Sodium bicarbonate was added and the phases were separated using a phase separator and concentrated under reduced pressure. The crude was purified on silica gel using 10% to 60% ethyl acetate in hexane to provide the title compound as an oil. MS: m/z=742.2 (MNa+).

Workup

  1. stirringby stirring overnight
  2. customthe phases were separated
  3. concentrationconcentrated under reduced pressure
  4. customThe crude was purified on silica gel using 10% to 60% ethyl acetate in hexane

Sources & evidence

ORD record
ord-a7cc23a65c9844afb88992099a8fd5d4
Source dataset
uspto-grants-2015_09
Patent number
US09133157B2

Reaction notes

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