Acetic Acid → HCID 67358208, compound

HRID 39436Notes

Reaction equation

HRID 39436 reaction equation
[CH3:1][O:2][C:3]1[CH:18]=[C:17]([C:19]([F:22])([F:21])[F:20])[CH:16]=[C:15]([S:23][CH3:24])[C:4]=1[C:5]([NH:7][CH:8]1[C:13](=O)[CH2:12][CH2:11][O:10][CH2:9]1)=[O:6].C(O)(=O)C.[NH:29]1[CH2:33][CH2:32][CH2:31][CH2:30]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>O1CCCC1>[CH3:1][O:2][C:3]1[CH:18]=[C:17]([C:19]([F:20])([F:22])[F:21])[CH:16]=[C:15]([S:23][CH3:24])[C:4]=1[C:5]([NH:7][C@H:8]1[C@@H:13]([N:29]2[CH2:33][CH2:32][CH2:31][CH2:30]2)[CH2:12][CH2:11][O:10][CH2:9]1)=[O:6]

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 31268PyrrolidineHCID 5049666Sodium triacetoxyborohydrideHCID 58381272HCID 58381272, compound2×

Product 1

HCID 67358208HCID 67358208, compoundYield 40%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

2-Methoxy-6-methylsulfanyl-N-(4-oxo-tetrahydro-pyran-3-yl)-4-trifluoromethyl-benzamide (intermediate C, 300 mg, 0.83 mmol) was dissolved in 5 mL tetrahydrofurane. Acetic acid (86 mg, 1.4 mmol) and pyrrolidine (70 mg, 0.99 mmol) were added and the reaction mixture was stirred 1 h at room temperature. Sodium triacetoxyborohydride (209 mg, 0.99 mmol) was added and stirring was continued at room temperature overnight. The mixture was extracted with 2N sodium carbonate solution and ethyl acetate. The combined organic phases were dried on sodium sulfate, filtered and evaporated. Purification of the residue by flash chromatography on silica gel (dichloromethane/methanol/ammonia 100:0:0→140:10:1) yielded cis-2-methoxy-6-methylsulfanyl-N-((3RS,4RS)-4-pyrrolidin-1-yl-tetrahydro-pyran-3-yl)-4-trifluoromethyl-benzamide as a light brown solid (80 mg, 40%), MS: m/e=419.1 [(M+H)] and trans-2-methoxy-6-methylsulfanyl-N-((3RS,4SR)-4-pyrrolidin-1-yl-tetrahydro-pyran-3-yl)-4-trifluoromethyl-benzamide as a light brown solid (25 mg, 12%), MS: m/e=419.1 [(M+H)+].

Workup

  1. stirringstirring
  2. waitwas continued at room temperature overnight
  3. extractionThe mixture was extracted with 2N sodium carbonate solution and ethyl acetate
  4. customThe combined organic phases were dried on sodium sulfate
  5. filtrationfiltered
  6. customevaporated
  7. customPurification of the residue by flash chromatography on silica gel (dichloromethane/methanol/ammonia 100:0:0→140:10:1)

Sources & evidence

ORD record
ord-8b88138625ff4e8180d1eb2de3adf7e1
Source dataset
uspto-grants-2013_09
Patent number
US08524909B2

Reaction notes

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