Triethylamine → (5R,7R)-4-chloro-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-7-yl 4-nitrobenzoate

HRID 521357Notes

Reaction equation

HRID 521357 reaction equation
[N+:1]([C:4]1[CH:12]=[CH:11][C:7]([C:8](Cl)=[O:9])=[CH:6][CH:5]=1)([O-:3])=[O:2].[Cl:13][C:14]1[C:15]2[C@H:22]([CH3:23])[CH2:21][CH:20]([OH:24])[C:16]=2[N:17]=[CH:18][N:19]=1.CCN(CC)CC>C(Cl)Cl.C([O-])(O)=O.[Na+]>[N+:1]([C:4]1[CH:12]=[CH:11][C:7]([C:8]([O:24][C@@H:20]2[C:16]3[N:17]=[CH:18][N:19]=[C:14]([Cl:13])[C:15]=3[C@H:22]([CH3:23])[CH2:21]2)=[O:9])=[CH:6][CH:5]=1)([O-:3])=[O:2].[N+:1]([C:4]1[CH:12]=[CH:11][C:7]([C:8]([O:24][C@H:20]2[C:16]3[N:17]=[CH:18][N:19]=[C:14]([Cl:13])[C:15]=3[C@H:22]([CH3:23])[CH2:21]2)=[O:9])=[CH:6][CH:5]=1)([O-:3])=[O:2]

Participants

7

Reactant 3

HCID 8471TriethylamineHCID 85024-Nitrobenzoyl chlorideHCID 86654856(5R)-4-chloro-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-7-ol

Product 2

HCID 86651804(5R,7R)-4-chloro-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-7-yl 4-nitrobenzoateYield 54%HCID 86658350(5R,7S)-4-chloro-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-7-yl 4-nitrobenzoateYield 36%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent2×HCID 516892Sodium BicarbonateSolvent

Procedure

Solid 4-nitrobenzoyl chloride (6.73 g, 36.3 mmol) was added to a stirred solution of (5R)-4-chloro-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-7-ol (6.09 g, 33.0 mmol) and NEt3 (5.98 mL, 42.9 mmol) in DCM (165 mL) at 0° C. The reaction was warmed to room temperature and then stirred at room temperature for 3 hours. The reaction was diluted with DCM and saturated aqueous NaHCO3. The combined extracts were washed with brine, dried MgSO4, filtered, and concentrated. The crude residue was chromatographed eluting with 10-14% EtOAc/hexane several times to give (5R,7S)-4-chloro-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-7-yl 4-nitrobenzoate (3.96 g, 36%) and (5R,7R)-4-chloro-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-7-yl 4-nitrobenzoate (5.92 g, 54%).

Workup

  1. washThe combined extracts were washed with brine, dried MgSO4
  2. filtrationfiltered
  3. concentrationconcentrated
  4. customThe crude residue was chromatographed
  5. washeluting with 10-14% EtOAc/hexane several times

Sources & evidence

ORD record
ord-0571358497884070bd05193955bd08b4
Source dataset
uspto-grants-2016_05
Patent number
US09328091B2

Reaction notes

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