1,3-Oxazolidine → tert-Butyl (S)-6-tert-butoxycarbonylamino-2-[((9S,12R)-9-isopropyl-11-oxo-2,7-dioxa-10-azabicyclo[12.2.2]octadeca-1(17),14(18),15-trien-12-ylsulfamoyl)amino]hexanoate

HRID 2040022Notes

Reaction equation

HRID 2040022 reaction equation
[C:1]([O:5][C:6]([NH:8][CH2:9][CH2:10][CH2:11][CH2:12][C@H:13]([NH:21][S:22](N1CCOC1=O)(=[O:24])=[O:23])[C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])=[O:7])([CH3:4])([CH3:3])[CH3:2].[NH2:31][C@@H:32]1[CH2:47][C:46]2=[CH:48][CH:49]=[C:43]([CH:44]=[CH:45]2)[O:42][CH2:41][CH2:40][CH2:39][CH2:38][O:37][CH2:36][C@H:35]([CH:50]([CH3:52])[CH3:51])[NH:34][C:33]1=[O:53].O1CCNC1>C(#N)C>[C:1]([O:5][C:6]([NH:8][CH2:9][CH2:10][CH2:11][CH2:12][C@H:13]([NH:21][S:22](=[O:23])(=[O:24])[NH:31][C@@H:32]1[CH2:47][C:46]2=[CH:45][CH:44]=[C:43]([CH:49]=[CH:48]2)[O:42][CH2:41][CH2:40][CH2:39][CH2:38][O:37][CH2:36][C@H:35]([CH:50]([CH3:51])[CH3:52])[NH:34][C:33]1=[O:53])[C:14]([O:16][C:17]([CH3:18])([CH3:19])[CH3:20])=[O:15])=[O:7])([CH3:3])([CH3:2])[CH3:4]

Participants

5

Reactant 3

HCID 5366831,3-OxazolidineHCID 58360483(9S,12R)-12-Amino-9-isopropyl-2,7-dioxa-10-azabicyclo[12.2.2]octadeca-1(17),14(18),15-trien-11-one2×HCID 67028806tert-butyl(S)-6-tert-butoxycarbonylamino-2-(2-oxooxazolidine-3-sulfonylamino)hexanoate

Product 1

HCID 67320439tert-Butyl (S)-6-tert-butoxycarbonylamino-2-[((9S,12R)-9-isopropyl-11-oxo-2,7-dioxa-10-azabicyclo[12.2.2]octadeca-1(17),14(18),15-trien-12-ylsulfamoyl)amino]hexanoateYield 14.6%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A solution of 387 mg (0.858 mmol) of tert-butyl (S)-6-tert-butoxycarbonylamino-2-(2-oxooxazolidine-3-sulfonylamino)hexanoate and 250 mg (0.780 mmol) of (9S,12R)-12-amino-9-isopropyl-2,7-dioxa-10-azabicyclo[12.2.2]octadeca-1(17),14(18),15-trien-11-one (compound 1-1E) in 15 ml of acetonitrile was stirred at 80° C. After 1 day (d), the same amount of the oxazolidine was again added, and the mixture was stirred for 1 d. The reaction mixture was then concentrated and the residue was purified by prep. HPLC. Product-containing fractions were combined, the acetonitrile was evaporated off, made slightly alkaline with sat. NaHCO3 solution and extracted several times with ethyl acetate. The combined organic phases were dried over Na2SO4, filtered and concentrated. 78 mg of the title compound were obtained.

Workup

  1. concentrationThe reaction mixture was then concentrated
  2. customthe residue was purified by prep
  3. customthe acetonitrile was evaporated off
  4. extractionextracted several times with ethyl acetate
  5. dry with materialThe combined organic phases were dried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-cf978afc64a640ab96697133bd334a61
Source dataset
uspto-grants-2013_11
Patent number
US08580777B2

Reaction notes

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