Ammonium Acetate → HCID 67957726, compound

HRID 1427774Notes

Reaction equation

HRID 1427774 reaction equation
ClC(Cl)(Cl)C[O:4][C:5]([C@@H:7]1[CH2:12][CH2:11][CH2:10][N:9]([C:13](=[O:49])[C@@H:14]([NH:30][C:31](=[O:48])[C@@H:32]([NH:36][C:37](=[O:47])[C@H:38]([CH3:46])[C@H:39]([O:44][CH3:45])[CH2:40][CH2:41][CH:42]=[CH2:43])[CH:33]([CH3:35])[CH3:34])[CH2:15][C:16]2[CH:21]=[CH:20][CH:19]=[C:18]([O:22][Si:23]([C:26]([CH3:29])([CH3:28])[CH3:27])([CH3:25])[CH3:24])[CH:17]=2)[NH:8]1)=[O:6].C([O-])(=O)C.[NH4+]>O1CCCC1.O.[Zn]>[C:26]([Si:23]([CH3:25])([CH3:24])[O:22][C:18]1[CH:17]=[C:16]([CH2:15][C@H:14]([NH:30][C:31](=[O:48])[C@@H:32]([NH:36][C:37](=[O:47])[C@H:38]([CH3:46])[C@H:39]([O:44][CH3:45])[CH2:40][CH2:41][CH:42]=[CH2:43])[CH:33]([CH3:34])[CH3:35])[C:13]([N:9]2[CH2:10][CH2:11][CH2:12][C@@H:7]([C:5]([OH:6])=[O:4])[NH:8]2)=[O:49])[CH:21]=[CH:20][CH:19]=1)([CH3:28])([CH3:27])[CH3:29]

Participants

6

Reactant 2

HCID 517165Ammonium AcetateHCID 67960499HCID 67960499, compound

Product 1

HCID 67957726HCID 67957726, compoundYield 102.3%

Reagents, catalysts & solvents 3

HCID 23994ZincCatalystHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of (S)-1-{(S)-3-[3-(tert-butyl-dimethyl-silanyloxy)-phenyl]-2-[(S)-2-((2R,3R)-3-methoxy-2-methyl-hept-6-enoylamino)-3-methyl-butyrylamino]-propionyl}-hexahydro-pyridazine-3-carboxylic acid 2,2,2-trichloro-ethyl ester (560 mg, 0.71 mmol) in tetrahydrofuran (16 mL) was added zinc dust (1.0 g, 15.6 mmol) followed by a solution of ammonium acetate (817 mg, 10.6 mmol) in water (7 mL). The reaction mixture was stirred vigorously at room temperature for 24 hours. The reaction mixture was filtered through celite and the filter pad was washed with dichloromethane. The aqueous layer was acidified to pH 4-5 with 2 M hydrochloric acid and the mixture was extracted with dichloromethane. The organic layers were combined and dried by passing through a hydrophobic frit. The solvent was evaporated and dried to afford (S)-1-{(S)-3-[3-(tert-butyl-dimethyl-silanyloxy)-phenyl]-2-[(S)-2-((2R,3R)-3-methoxy-2-methyl-hept-6-enoylamino)-3-methyl-butyrylamino]-propionyl}-hexahydro-pyridazine-3-carboxylic acid (480 mg) which was used crude in the next step. LCMS (m/z) 661 [M+H], Tr=5.46 min.

Workup

  1. filtrationThe reaction mixture was filtered through celite
  2. washthe filter pad was washed with dichloromethane
  3. extractionthe mixture was extracted with dichloromethane
  4. customdried
  5. customThe solvent was evaporated
  6. customdried

Sources & evidence

ORD record
ord-69d5977fe4c448e5aa607b754e90375b
Source dataset
uspto-grants-2015_01
Patent number
US08933015B2

Reaction notes

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