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Hydrochloric Acid → 1-[3-(1,3-Dihydroxy-3-m-tolyl-propyl)-4-methoxy-benzoylamino]-cycloheptanecarboxylic acid methyl ester

HRID 1475716
Notes
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Reaction equation

HRID 1475716 reaction equation
CO[C:3](=[O:15])[C:4]1[CH:9]=[CH:8][C:7]([O:10][CH3:11])=[C:6]([C:12](=[O:14])[CH3:13])[CH:5]=1.C([N-:19][CH:20]([CH3:22])[CH3:21])(C)C.[Li+].[CH3:24][C:25]1[CH:26]=[C:27]([CH:30]=[CH:31][CH:32]=1)[CH:28]=[O:29].Cl.[BH4-].[Na+].C[C:37](=[O:41])[O:38][CH2:39]C>C1COCC1>[CH3:39][O:38][C:37]([C:20]1([NH:19][C:3](=[O:15])[C:4]2[CH:9]=[CH:8][C:7]([O:10][CH3:11])=[C:6]([CH:12]([OH:14])[CH2:13][CH:28]([OH:29])[C:27]3[CH:26]=[C:25]([CH3:24])[CH:32]=[CH:31][CH:30]=3)[CH:5]=2)[CH2:21][CH2:6][CH2:5][CH2:4][CH2:3][CH2:22]1)=[O:41]
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

8

Reactant 6

HCID 313Hydrochloric AcidHCID 8857Ethyl AcetateHCID 121053-MethylbenzaldehydeHCID 2724682Lithium diisopropylamideHCID 4311764Sodium borohydrideHCID 10798398Methyl 3-acetyl-4-methoxybenzoate

Product 1

HCID 67169537
1-[3-(1,3-Dihydroxy-3-m-tolyl-propyl)-4-methoxy-benzoylamino]-cycloheptanecarboxylic acid methyl ester

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

3-Acetyl-4-methoxy-benzoic acid methyl ester (150 mg, 0.720 mmol) was dissolved in THF (3 ml), cooled to −78° C., and a freshly prepared solution of lithium diisopropylamide (obtained by addition of n-butyllithium in n-hexane (0.317 ml, 2.5 M solution) to diisopropylamine (80.1 mg, 0.792 mmol) in THF (3 ml) at 0° C. and stirring for 10 min) was slowly added with stirring. After 10 min, 3-methylbenzaldehyde (86.5 mg, 0.720 mmol) was added at −78° C. After 30 min at −78° C., 2 N hydrochloric acid and EA were added, the cooling bath was removed, the mixture was brought to room temperature. The phases were separated, the aqueous phase was extracted three times with EA, the combined organic phases were dried over sodium chloride, decanted and evaporated to dryness. The residue was dissolved in methanol (5 ml), sodium borohydride (28.7 mg, 0.761 mmol) was added, and the mixture was stirred at room temperature for 30 min. The mixture was evaporated to dryness and the residue was purified by silica gel chromatography (HEP/EA gradient) to give 140 mg of the title compound as a mixture of diastereomers.

Workup

  1. waitAfter 30 min at −78° C.
  2. customthe cooling bath was removed
  3. customwas brought to room temperature
  4. customThe phases were separated
  5. extractionthe aqueous phase was extracted three times with EA
  6. dry with materialthe combined organic phases were dried over sodium chloride
  7. customdecanted
  8. customevaporated to dryness
  9. dissolutionThe residue was dissolved in methanol (5 ml)
  10. stirringthe mixture was stirred at room temperature for 30 min
  11. customThe mixture was evaporated to dryness
  12. customthe residue was purified by silica gel chromatography (HEP/EA gradient)

Sources & evidence

ORD record
ord-ff8b2aa71ba347948a3ce79056227a5c
Source dataset
uspto-grants-2015_04
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US09018383B2

Reaction notes

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On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes