Hydrochloric Acid → HCID 86653406, compound

HRID 1915977Notes

Reaction equation

HRID 1915977 reaction equation
[Li+].[OH-:2].C[O:4][C:5](=O)[CH2:6][NH:7][C:8]([C:10]1([NH:13][C:14](=[O:78])[C@H:15]([NH:37][C:38](=[O:77])[C@H:39]([NH:47][C:48](=[O:76])[CH2:49][C@H:50](O)/[CH:51]=[CH:52]/[CH2:53][CH2:54][S:55][C:56]([C:69]2[CH:74]=[CH:73][CH:72]=[CH:71][CH:70]=2)([C:63]2[CH:68]=[CH:67][CH:66]=[CH:65][CH:64]=2)[C:57]2[CH:62]=[CH:61][CH:60]=[CH:59][CH:58]=2)[CH2:40][C:41]2[CH:46]=[CH:45][N:44]=[CH:43][CH:42]=2)[CH2:16][S:17][C:18]([C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=2)([C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[CH2:12][CH2:11]1)=[O:9].Cl.CC1C=CC=C([N+]([O-])=O)C=1C(OC(=O)C1C([N+]([O-])=O)=CC=CC=1C)=O>O.C1COCC1.[Cl-].[Na+].O.C(Cl)Cl.C1COCC1.CN(C)C1C=CN=CC=1.C(Cl)Cl.CCOC(C)=O>[N:44]1[CH:45]=[CH:46][C:41]([CH2:40][C@H:39]2[NH:47][C:48](=[O:76])[CH2:49][C@H:50](/[CH:51]=[CH:52]/[CH2:53][CH2:54][S:55][C:56]([C:57]3[CH:58]=[CH:59][CH:60]=[CH:61][CH:62]=3)([C:63]3[CH:64]=[CH:65][CH:66]=[CH:67][CH:68]=3)[C:69]3[CH:74]=[CH:73][CH:72]=[CH:71][CH:70]=3)[O:2][C:5](=[O:4])[CH2:6][NH:7][C:8](=[O:9])[C:10]3([CH2:12][CH2:11]3)[NH:13][C:14](=[O:78])[C@@H:15]([CH2:16][S:17][C:18]([C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=3)([C:31]3[CH:32]=[CH:33][CH:34]=[CH:35][CH:36]=3)[C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)[NH:37][C:38]2=[O:77])=[CH:42][CH:43]=1

Participants

12

Reactant 4

HCID 313Hydrochloric AcidHCID 3939Lithium HydroxideHCID 104726482-Methyl-6-nitrobenzoic anhydrideHCID 86653407HCID 86653407, compound

Product 1

HCID 86653406HCID 86653406, compoundYield 54.5%

Reagents, catalysts & solvents 7

HCID 142844-(Dimethylamino)pyridineCatalystHCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolventHCID 21919333Tetrahydrofurane dichloromethaneSolventHCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
0 °C

Procedure

LiOH (13 mg, 0.54 mmol) in water (2 mL) was added to 4 (384 mg, 0.36 mmol) in THF (8 mL) at 0° C. After 1.5 h of stirring at 0° C. the reaction mixture was neutralized with aqueous 0.5 M HCl then brine (50 mL) and EtOAc (50 mL) were added. The phases were separated and the aqueous phase was extracted with EtOAc (3×10 mL). The organic phases were combined, dried over MgSO4, filtered then concentrated under reduced pressure. The crude product was dried under high vacuum before to be use for the next step. The crude carboxylic acid in CH2Cl2/THF (250 mL, 12:1 v/v) was added dropwise over a period of 3 h to 2-methyl-6-nitrobenzoic anhydride (149 mg, 0.43 mmol) and 4-(dimethylamino)pyridine (105 mg, 0.86 mmol) in CH2Cl2 (120 mL) at rt under Ar(g). After 19 h the reaction mixture was concentrated under reduced pressure and the residue was purified by silica gel column chromatography eluting with CH2Cl2/CH3OH (100:2 then 100:10) to yield 5 as a white solid (203 mg, 54%).

Workup

  1. customThe phases were separated
  2. extractionthe aqueous phase was extracted with EtOAc (3×10 mL)
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. concentrationthen concentrated under reduced pressure
  6. dry with materialThe crude product was dried under high vacuum before
  7. concentrationAfter 19 h the reaction mixture was concentrated under reduced pressure
  8. customthe residue was purified by silica gel column chromatography
  9. washeluting with CH2Cl2/CH3OH (100:2

Sources & evidence

ORD record
ord-817bf1f4f4d44066a482855035561229
Source dataset
uspto-grants-2013_12
Patent number
US08614193B2

Reaction notes

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