Triphenylphosphine → (R)-tert-butyl 2-(4-chlorophenyl)-2-(4-(5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)phenoxy)ethyl(isopropyl)carbamate

HRID 340124Notes

Reaction equation

HRID 340124 reaction equation
N(C(OCC)=O)=NC(OCC)=O.[Cl:13][C:14]1[CH:19]=[CH:18][C:17]([CH:20]([OH:33])[CH2:21][N:22]([CH:30]([CH3:32])[CH3:31])[C:23](=[O:29])[O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[CH:16][CH:15]=1.[CH3:34][C@H:35]1[C:43]2[C:42]([C:44]3[CH:49]=[CH:48][C:47](O)=[CH:46][CH:45]=3)=[N:41][CH:40]=[N:39][C:38]=2[CH2:37][CH2:36]1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>O1CCCC1.O>[Cl:13][C:14]1[CH:19]=[CH:18][C:17]([C@@H:20]([O:33][C:47]2[CH:48]=[CH:49][C:44]([C:42]3[C:43]4[CH:35]([CH3:34])[CH2:36][CH2:37][C:38]=4[N:39]=[CH:40][N:41]=3)=[CH:45][CH:46]=2)[CH2:21][N:22]([CH:30]([CH3:31])[CH3:32])[C:23](=[O:29])[O:24][C:25]([CH3:26])([CH3:27])[CH3:28])=[CH:16][CH:15]=1

Participants

7

Reactant 4

HCID 11776Triphenylphosphine2×HCID 220568ethyl N-ethoxycarbonyliminocarbamate2×HCID 67438323Tert-butyl 2-(4-chlorophenyl)-2-hydroxyethyl(isopropyl)carbamate2×HCID 136385952(R)-4-(5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)phenol

Product 1

HCID 67436772(R)-tert-butyl 2-(4-chlorophenyl)-2-(4-(5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)phenoxy)ethyl(isopropyl)carbamateYield 7.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

Diethyl azodicarboxylate (0.166 mL, 1.05 mmol) was added slowly to a solution of tert-butyl 2-(4-chlorophenyl)-2-hydroxyethyl(isopropyl)carbamate (265 mg, 0.843 mmol), (R)-4-(5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)phenol (159 mg, 0.703 mmol), and triphenylphosphine (276 mg, 1.05 mmol) in tetrahydrofuran (7.0 mL) at −30° C. (bath). The mixture was allowed to warm up to room temperature and stirred overnight. Most of the starting material remained. Triphenylphosphine (276 mg, 1.05 mmol) was added. The contents were cooled at −30° C. Diethyl azodicarboxylate (0.166 mL, 1.05 mmol) was added. The mixture was stirred at room temperature for 4 hours. tert-Butyl 2-(4-chlorophenyl)-2-hydroxyethyl(isopropyl)carbamate (265 mg, 0.843 mmol) was added. The mixture was stirred at room temperature overnight. EtOAC (10 mL) and water (10 mL) were added. The organic layer was separated. The aqueous layer was extracted with EtOAc (2×10 mL). The combined organic solutions were dried (Na2SO4). The crude was purified by flash chromatography to give (R)-tert-butyl 2-(4-chlorophenyl)-2-(4-(5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)phenoxy)ethyl(isopropyl)carbamate (26 mg, 7%).

Workup

  1. temperatureThe contents were cooled at −30° C
  2. stirringThe mixture was stirred at room temperature for 4 hours
  3. stirringThe mixture was stirred at room temperature overnight
  4. customThe organic layer was separated
  5. extractionThe aqueous layer was extracted with EtOAc (2×10 mL)
  6. dry with materialThe combined organic solutions were dried (Na2SO4)
  7. customThe crude was purified by flash chromatography

Sources & evidence

ORD record
ord-839448fcf9a14975888477ac9eb01940
Source dataset
uspto-grants-2014_11
Patent number
US08895566B2

Reaction notes

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