Tricyclo(3.3.1.1'3,7)dec-1-ylmethanol → tert-butyl (2S)-2-(1-adamantylmethyloxycarbonylamino)-3-(4-(3-ethoxycarbonylpropyloxy)phenyl)propionate

HRID 1394013Notes

Reaction equation

HRID 1394013 reaction equation
[C:1](N1C=CN=C1)(N1C=CN=C1)=[O:2].[OH:13][CH2:14][C:15]12[CH2:24][CH:19]3[CH2:20][CH:21]([CH2:23][CH:17]([CH2:18]3)[CH2:16]1)[CH2:22]2.[NH2:25][C@@H:26]([CH2:34][C:35]1[CH:40]=[CH:39][C:38]([O:41][CH2:42][CH2:43][CH2:44][C:45]([O:47][CH2:48][CH3:49])=[O:46])=[CH:37][CH:36]=1)[C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28].C(N(C(C)C)CC)(C)C>O1CCCC1.C(OCC)(=O)C>[C:15]12([CH2:14][O:13][C:1]([NH:25][C@@H:26]([CH2:34][C:35]3[CH:36]=[CH:37][C:38]([O:41][CH2:42][CH2:43][CH2:44][C:45]([O:47][CH2:48][CH3:49])=[O:46])=[CH:39][CH:40]=3)[C:27]([O:29][C:30]([CH3:32])([CH3:33])[CH3:31])=[O:28])=[O:2])[CH2:24][CH:19]3[CH2:18][CH:17]([CH2:23][CH:21]([CH2:20]3)[CH2:22]1)[CH2:16]2

Participants

7

Reactant 4

HCID 64556Tricyclo(3.3.1.1'3,7)dec-1-ylmethanolHCID 682631,1'-CarbonyldiimidazoleHCID 81531DiisopropylethylamineHCID 15512208tert-Butyl (2S)-2-amino-3-(4-(3-ethoxycarbonylpropyloxy)phenyl)propionate

Product 1

HCID 15512209tert-butyl (2S)-2-(1-adamantylmethyloxycarbonylamino)-3-(4-(3-ethoxycarbonylpropyloxy)phenyl)propionateYield 85.2%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

892 mg (5.5 mmol) of carbonyldiimidazole (CDl) were added to a solution of 830 mg (5 mmol) of 1-hydroxymethyladamantane in 10 ml of tetrahydrofuran and the mixture was stirred overnight at RT. It was then treated with 1 g (2.57 mmol) of tertbutyl (2S)-2-amino-3-(4-(3-ethoxycarbonyl-propyloxy)phenyl)propionate and 442 μl (2.57 mmol) of diisopropylethylamine (DIPEA) and the mixture was stirred overnight at 50° C. After cooling, it was taken up in ethyl acetate and the organic phase was washed successively with 3% strength citric acid solution, sodium hydrogencarbonate solution, 3×H2O and saturated NaCl solution. The organic phase was dried using MgSO4, the drying agent was filtered off and the filtrate was concentrated. The residue was chromatographed on silica gel using CH2Cl2/CH3OH (99/1). 1.19 g (85%) of an oil were obtained, which was employed without further purification for the synthesis of (4.4).

Workup

  1. stirringthe mixture was stirred overnight at 50° C
  2. temperatureAfter cooling
  3. washthe organic phase was washed successively with 3% strength citric acid solution, sodium hydrogencarbonate solution, 3×H2O and saturated NaCl solution
  4. customThe organic phase was dried
  5. filtrationthe drying agent was filtered off
  6. concentrationthe filtrate was concentrated
  7. customThe residue was chromatographed on silica gel

Sources & evidence

ORD record
ord-03567993797f48239c8349d4d635abde
Source dataset
uspto-grants-2008_03
Patent number
US07348333B2

Reaction notes

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