Hydrochloric Acid → HCID 86653401, compound

HRID 1915970Notes

Reaction equation

HRID 1915970 reaction equation
[Li+].[OH-].C[O:4][C:5](=[O:75])[CH2:6][NH:7][C:8](=[O:74])[C@H:9]([NH:13][C:14](=[O:73])[C@H:15]([NH:37][C:38](=[O:72])[C:39]([NH:42][C:43](=[O:71])[CH2:44][C@H:45](O)/[CH:46]=[CH:47]/[CH2:48][CH2:49][S:50][C:51]([C:64]1[CH:69]=[CH:68][CH:67]=[CH:66][CH:65]=1)([C:58]1[CH:63]=[CH:62][CH:61]=[CH:60][CH:59]=1)[C:52]1[CH:57]=[CH:56][CH:55]=[CH:54][CH:53]=1)([CH3:41])[CH3:40])[CH2:16][S:17][C:18]([C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1)([C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1)[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)[CH:10]([CH3:12])[CH3:11].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>[CH:10]([C@H:9]1[NH:13][C:14](=[O:73])[C@@H:15]([CH2:16][S:17][C:18]([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)([C:31]2[CH:32]=[CH:33][CH:34]=[CH:35][CH:36]=2)[C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[NH:37][C:38](=[O:72])[C:39]([CH3:40])([CH3:41])[NH:42][C:43](=[O:71])[CH2:44][C@H:45](/[CH:46]=[CH:47]/[CH2:48][CH2:49][S:50][C:51]([C:64]2[CH:65]=[CH:66][CH:67]=[CH:68][CH:69]=2)([C:58]2[CH:59]=[CH:60][CH:61]=[CH:62][CH:63]=2)[C:52]2[CH:57]=[CH:56][CH:55]=[CH:54][CH:53]=2)[O:75][C:5](=[O:4])[CH2:6][NH:7][C:8]1=[O:74])([CH3:12])[CH3:11]

Participants

12

Reactant 4

HCID 313Hydrochloric AcidHCID 3939Lithium HydroxideHCID 104726482-Methyl-6-nitrobenzoic anhydrideHCID 86653400HCID 86653400, compound

Product 1

HCID 86653401HCID 86653401, compoundYield 47.4%

Reagents, catalysts & solvents 7

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

Conditions

Temperature
0 °C

Procedure

LiOH (9 mg, 0.37 mmol) in water (2 mL) was added to 4 (255 mg, 0.25 mmol) in THF (8 mL) at 0° C. After 45 minutes of stirring at 0° C. the reaction mixture was neutralized with aqueous 0.5M HCl, then brine (40 mL) and EtOAc (40 mL) were added. The phases were separated and the aqueous phase was extracted with EtOAc (20 mL). The organic extracts were combined, dried over MgSO4, filtered then concentrated under reduced pressure. The crude product was dried under high vacuum before being used in the next step. The crude carboxylic acid in CH2Cl2/THF (200 mL, 12:1 v/v) was added dropwise over a period of 3 h to 2-methyl-6-nitrobenzoic anhydride (103 mg, 0.30 mmol) and 4-(dimethylamino)pyridine (73 mg, 0.60 mmol) in CH2Cl2 (50 mL) at rt under Ar(g). After 15 h, the reaction mixture was concentrated under reduced pressure and the residue was purified by silica gel column chromatography eluting with CH2Cl2/isopropanol (100:2.5 then 100:5) to yield 5 as a white solid (117 mg, 47%).

Workup

  1. customThe phases were separated
  2. extractionthe aqueous phase was extracted with EtOAc (20 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
  7. waitAfter 15 h
  8. concentrationthe reaction mixture was concentrated under reduced pressure
  9. customthe residue was purified by silica gel column chromatography
  10. washeluting with CH2Cl2/isopropanol (100:2.5

Sources & evidence

ORD record
ord-44877492d2564af8b54cdbb4979a596b
Source dataset
uspto-grants-2013_12
Patent number
US08614193B2

Reaction notes

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