Hydrochloric Acid → HCID 86678284, compound

HRID 2407887Notes

Reaction equation

HRID 2407887 reaction equation
[CH2:1]([O:3][P:4]([CH2:9][CH2:10][CH2:11][O:12][CH2:13][C@@H:14]([NH:16][C:17](=[O:23])OC(C)(C)C)[CH3:15])([O:6][CH2:7][CH3:8])=[O:5])[CH3:2].Cl.O1CCOCC1.[C:31]([O:44][C@H:45]([CH2:71][O:72][C:73](=[O:85])[CH2:74][CH2:75][CH2:76][CH2:77][CH2:78][CH2:79][CH2:80][CH2:81][CH2:82][CH2:83][CH3:84])[CH2:46][S:47][CH2:48][C@@H:49](C(O)=O)[NH:50][C:51](=[O:67])[O:52][CH2:53][CH:54]1[C:66]2[CH:65]=[CH:64][CH:63]=[CH:62][C:61]=2[C:60]2[C:55]1=[CH:56][CH:57]=[CH:58][CH:59]=2)(=[O:43])[CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][CH2:37][CH2:38][CH2:39][CH2:40][CH2:41][CH3:42].CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>C(Cl)Cl>[CH2:7]([O:6][P:4]([CH2:9][CH2:10][CH2:11][O:12][CH2:13][C@H:14]([CH3:15])[NH:16][C:17](=[O:23])[C@@H:49]([NH:50][C:51]([O:52][CH2:53][CH:54]1[C:55]2[CH:56]=[CH:57][CH:58]=[CH:59][C:60]=2[C:61]2[C:66]1=[CH:65][CH:64]=[CH:63][CH:62]=2)=[O:67])[CH2:48][S:47][CH2:46][C@H:45]([O:44][C:31](=[O:43])[CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][CH2:37][CH2:38][CH2:39][CH2:40][CH2:41][CH3:42])[CH2:71][O:72][C:73](=[O:85])[CH2:74][CH2:75][CH2:76][CH2:77][CH2:78][CH2:79][CH2:80][CH2:81][CH2:82][CH2:83][CH3:84])(=[O:5])[O:3][CH2:1][CH3:2])[CH3:8]

Participants

8

Reactant 6

HCID 313Hydrochloric AcidHCID 312751,4-DioxaneHCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 67414703(5R,9R)-9-(dodecanoyloxy)-1-(9H-fluoren-9-yl)-3,12-dioxo-2,11-dioxa-7-thia-4-azatricosane-5-carboxylic acidHCID 86678283HCID 86678283, compound

Product 1

HCID 86678284HCID 86678284, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of (S)-tert-butyl 1-(3-(diethoxyphosphoryl)propoxy)propan-2-ylcarbamate (1.3 eq, from the previous step) in DCM (0.22 M) at room temperature was added a solution of 4 M HCl in dioxane (20 eq). The reaction was stirred for 1.5 hours. The reaction mixture was concentrated en vaccuo to give an oil which was evaporated under high vacuum briefly. This residue was taken up in DCM (0.1M). To this solution was added (5R,9R)-9-(dodecanoyloxy)-1-(9H-fluoren-9-yl)-3,12-dioxo-2,11-dioxa-7-thia-4-azatricosane-5-carboxylic acid (6, 1 eq), HBTU (1.2 eq), and DIEA (4 eq). The reaction was stirred at room temperature for 2 hours. The mixture was purified by flash chromatography on a COMBIFLASH® system (ISCO) using a gradient of 0-100% ethyl acetate in hexanes and then 100% ethyl acetate to give the product as an oil.

Workup

  1. concentrationThe reaction mixture was concentrated en vaccuo
  2. customto give an oil which
  3. customwas evaporated under high vacuum briefly
  4. stirringThe reaction was stirred at room temperature for 2 hours
  5. customThe mixture was purified by flash chromatography on a COMBIFLASH® system (ISCO)

Sources & evidence

ORD record
ord-f68b2061c943434bbfc9592b23d00a47
Source dataset
uspto-grants-2014_08
Patent number
US08808703B2

Reaction notes

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