Cyclopropanecarboxaldehyde → 4-((3,5-Bis(trifluoromethyl)benzyloxy)methyl)-1-(cyclopropylmethyl)-4-phenylazepane

HRID 11222

Reaction equation

HRID 11222 reaction equation
[F:1][C:2]([F:30])([F:29])[C:3]1[CH:4]=[C:5]([CH:22]=[C:23]([C:25]([F:28])([F:27])[F:26])[CH:24]=1)[CH2:6][O:7][CH2:8][C:9]1([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[CH2:15][CH2:14][CH2:13][NH:12][CH2:11][CH2:10]1.[CH:31]1([CH:34]=O)[CH2:33][CH2:32]1.C([BH3-])#N.[Na+]>CO.FC(F)(F)C(O)=O>[F:30][C:2]([F:29])([F:1])[C:3]1[CH:4]=[C:5]([CH:22]=[C:23]([C:25]([F:28])([F:27])[F:26])[CH:24]=1)[CH2:6][O:7][CH2:8][C:9]1([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[CH2:15][CH2:14][CH2:13][N:12]([CH2:34][CH:31]2[CH2:33][CH2:32]2)[CH2:11][CH2:10]1

Participants

6

Reactant 3

HCID 123114CyclopropanecarboxaldehydeHCID 5003444Sodium cyanoborohydrideHCID 116261604-((3,5-Bis(trifluoromethyl)benzyloxy)methyl)-4-phenylazepane

Product 1

HCID 219731184-((3,5-Bis(trifluoromethyl)benzyloxy)methyl)-1-(cyclopropylmethyl)-4-phenylazepaneYield 41.5%

Reagents, catalysts & solvents 2

HCID 6422Trifluoroacetic acidCatalystHCID 887MethanolSolvent

Procedure

Mixture of isomer A of 4-((3,5-bis(trifluoromethyl)benzyloxy)methyl)-4-phenylazepane (3 mg) and cyclopropanecarbaldehyde (1.4 mg) in methanol (0.15 mL) was stirred at room temperature for 0.5 hr, then sodium cyanoborohydride (1.0 M solution in THF, 0.02 mL) was added followed by 1 drop of trifluoroacetic acid. The mixture was stirred at room temperature for overnight and concentrated under vacuum. Then saturated sodium bicarbonate and dichloromethane was added to the mixture and the organic layer was separated. The aqueous layer was extracted with dichloromethane 2 times and the combined organic layers were dried over magnesium sulfate, filtered and concentrated under vacuum to give the product as a clear sticky oil (1.4 mg, 41% yield).

Workup

  1. stirringThe mixture was stirred at room temperature for overnight
  2. concentrationconcentrated under vacuum
  3. additionThen saturated sodium bicarbonate and dichloromethane was added to the mixture
  4. customthe organic layer was separated
  5. extractionThe aqueous layer was extracted with dichloromethane 2 times
  6. dry with materialthe combined organic layers were dried over magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-55ba5bde656147629274f122dc38c215
Source dataset
uspto-grants-2006_08
Patent number
US07098203B2

Linked notes

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