Acetic Acid → 4-[2-Amino-2-(3-chloro-phenyl)-propylamino]-adamantane-1-carboxylic acid methyl ester

HRID 1092361Notes

Reaction equation

HRID 1092361 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:8]([NH2:12])([CH3:11])[CH2:9][NH2:10])[CH:5]=[CH:6][CH:7]=1.[CH3:13][O:14][C:15]([C:17]12[CH2:26][CH:21]3[CH2:22][CH:23]([CH2:25][CH:19]([C:20]3=O)[CH2:18]1)[CH2:24]2)=[O:16].C(O)(=O)C.[BH4-].[Na+]>C(O)C.O>[CH3:13][O:14][C:15]([C:17]12[CH2:26][CH:21]3[CH2:22][CH:23]([CH2:25][CH:19]([CH:20]3[NH:10][CH2:9][C:8]([NH2:12])([C:4]3[CH:5]=[CH:6][CH:7]=[C:2]([Cl:1])[CH:3]=3)[CH3:11])[CH2:18]1)[CH2:24]2)=[O:16]

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 4078246Methyl 4-oxoadamantane-1-carboxylateHCID 4311764Sodium borohydrideHCID 574956392-(3-Chloro-phenyl)-propane-1,2-diamine

Product 1

HCID 574956404-[2-Amino-2-(3-chloro-phenyl)-propylamino]-adamantane-1-carboxylic acid methyl esterYield 86.5%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 962WaterSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 2-(3-chloro-phenyl)-propane-1,2-diamine (3.4 g) and 4-oxo-adamantane-1-carboxylic acid methyl ester (CAS 56674-88-5, 3.85 g) in ethanol (50 mL) was added acetic acid (0.7 mL) and reaction mixture was refluxed for 4 h, after which it was cooled to 0° C. and NaBH4 was added. The reaction mixture was then slowly brought to room temperature and left at stirring for 17 h. The reaction was monitored by TLC. After completion, water (30 mL) was slowly added. The reaction mixture was concentrated at reduced pressure to remove the ethanol. The aqueous layer was extracted with DCM (3×50 mL) and the organic layers were then dried over Na2SO4 and then concentrated to get crude desired 4-[2-amino-2-(3-chloro-phenyl)-propylamino]-adamantane-1-carboxylic acid methyl ester (6 g) as a mixture of E/Z isomers. The compound was used in the next step without further purification. MS (ESI): 377.4 (MH+).

Workup

  1. temperaturewas refluxed for 4 h
  2. customwas then slowly brought to room temperature
  3. waitleft
  4. concentrationThe reaction mixture was concentrated at reduced pressure
  5. customto remove the ethanol
  6. extractionThe aqueous layer was extracted with DCM (3×50 mL)
  7. dry with materialthe organic layers were then dried over Na2SO4
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-577800aa0fcd43729be1d65a83bb0007
Source dataset
uspto-grants-2012_03
Patent number
US08129423B2

Reaction notes

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