Acetic Acid → HCID 58997317, compound

HRID 1716917Notes

Reaction equation

HRID 1716917 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([NH:8][C:9](=[O:18])[C:10]2[CH:15]=[CH:14][C:13]([F:16])=[CH:12][C:11]=2[Cl:17])[CH:5]=[CH:6][CH:7]=1.[C:19]([O:23][C:24]([N:26]1[CH2:31][CH2:30][C:29](=O)[CH2:28][C@@H:27]1[CH3:33])=[O:25])([CH3:22])([CH3:21])[CH3:20].C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>O1CCCC1.CO>[C:19]([O:23][C:24]([N:26]1[CH2:31][CH2:30][C@H:29]([NH:1][C:2]2[CH:7]=[CH:6][CH:5]=[C:4]([NH:8][C:9](=[O:18])[C:10]3[CH:15]=[CH:14][C:13]([F:16])=[CH:12][C:11]=3[Cl:17])[CH:3]=2)[CH2:28][C@@H:27]1[CH3:33])=[O:25])([CH3:22])([CH3:20])[CH3:21]

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 5049666Sodium triacetoxyborohydrideHCID 11401606tert-butyl (2S)-2-methyl-4-oxopiperidine-1-carboxylateHCID 16775600N-(3-Aminophenyl)-2-chloro-4-fluorobenzamide

Product 1

HCID 58997317HCID 58997317, compoundYield 46.1%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

Dissolve N-(3-amino-phenyl)-2-chloro-4-fluoro-benzamide (Preparation 1, 200 mg, 0.756 mmol) and (2S)-2-methyl-4-oxo-piperidine-1-carboxylic acid tert-butyl ester (161 mg, 0.756 mmol) in tetrahydrofuran (5 mL). Add acetic acid (52 μL, 0.907 mmol) and sodium triacetoxyborohydride (192 mg, 0.907 mmol) and stir at room temperature for 18 hr. Heat the reaction to 45° C. for 4 hr. Cool the reaction to room temperature and load onto an SCX column with methanol. Wash the column with methanol, flush with 2M ammonia in methanol, and concentrate in vacuo. Purify by column chromatography (20%-75% ethyl acetate/hexane) to yield 161 mg (46%) of the title compound. Mass spectrum (ion spray): m/z 462.4 (M+1); 1H NMR: δ (CDCl3, ppm) 7.76 (m, 2H), 7.20 (m, 1H), 7.15 (m, 1H), 7.10 (m, 1H), 6.70 (d, J=7.6 Hz, 1H), 6.40 (d, J=8.4 Hz, 1H), 4.20 (m, 1H), 3.82 (m, 2H), 3.67 (bs, 1H), 3.20 (m, 1H), 2.00 (m, 2H), 1.65 (m, 2H), 1.47 (s, 9H), 1.27, (m, 4H).

Workup

  1. temperatureHeat
  2. customthe reaction to 45° C. for 4 hr
  3. temperatureCool
  4. customthe reaction to room temperature
  5. washWash the column with methanol
  6. customflush with 2M ammonia in methanol
  7. concentrationconcentrate in vacuo
  8. customPurify by column chromatography (20%-75% ethyl acetate/hexane)

Sources & evidence

ORD record
ord-baa412e9214d44f38e569acfefe74fae
Source dataset
uspto-grants-2010_09
Patent number
US07803813B2

Reaction notes

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