Triethylamine → tert-butyl 4-((5R,7R)-5-methyl-7-(4-nitrobenzoyloxy)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)piperazine-1-carboxylate

HRID 75404노트

반응식

HRID 75404 반응식
[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].[OH:13][CH:14]1[C:18]2[N:19]=[CH:20][N:21]=[C:22]([N:23]3[CH2:28][CH2:27][N:26]([C:29]([O:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:30])[CH2:25][CH2:24]3)[C:17]=2[C@H:16]([CH3:36])[CH2:15]1.CCN(CC)CC.C([O-])(O)=O.[Na+]>C(Cl)Cl>[CH3:36][C@H:16]1[C:17]2[C:22]([N:23]3[CH2:28][CH2:27][N:26]([C:29]([O:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:30])[CH2:25][CH2:24]3)=[N:21][CH:20]=[N:19][C:18]=2[C@H:14]([O:13][C:8](=[O:9])[C:7]2[CH:6]=[CH:5][C:4]([N+:1]([O-:3])=[O:2])=[CH:12][CH:11]=2)[CH2:15]1.[CH3:36][C@H:16]1[C:17]2[C:22]([N:23]3[CH2:28][CH2:27][N:26]([C:29]([O:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:30])[CH2:25][CH2:24]3)=[N:21][CH:20]=[N:19][C:18]=2[C@@H:14]([O:13][C:8](=[O:9])[C:7]2[CH:6]=[CH:5][C:4]([N+:1]([O-:3])=[O:2])=[CH:12][CH:11]=2)[CH2:15]1

참가 물질

7

반응물 4

HCID 8471TriethylamineHCID 85024-Nitrobenzoyl chlorideHCID 516892Sodium BicarbonateHCID 59580348(R)-tert-butyl 4-(7-hydroxy-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)piperazine-1-carboxylate

생성물 2

HCID 59580346tert-butyl 4-((5R,7R)-5-methyl-7-(4-nitrobenzoyloxy)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)piperazine-1-carboxylateHCID 59580349tert-butyl 4-((5R,7S)-5-methyl-7-(4-nitrobenzoyloxy)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)piperazine-1-carboxylate

시약·촉매·용매 1

HCID 6344Dichloromethane용매

실험 절차

4-Nitrobenzoyl chloride (15.78 g, 85.03 mmol) was added to a 0° C. solution of (R)-tert-butyl 4-(7-hydroxy-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)piperazine-1-carboxylate (25.85 g, 77.30 mmol) and NEt3 (11.73 g, 16.16 mL, 115.9 mmol) in DCM (400 mL). The reaction mixture was stirred for 5 minutes. The mixture was then warmed to room temperature and stirred overnight (17 hours), after which saturated NaHCO3 was added. The reaction mixture was stirred for 10 minutes and transferred to a separatory funnel. The organic layers were collected, and the aqueous extracts were washed with DCM (2×). The combined organic extracts were dried (Na2SO4), filtered, and concentrated. The crude was flashed on silica loaded with 7:1 hexanes:ethyl acetate (gradient 5:1 hexanes:ethyl acetate to 2:1 hexanes:ethyl acetate to 1:1 hexanes:ethyl acetate). Some clean tert-butyl 4-((5R,7R)-5-methyl-7-(4-nitrobenzoyloxy)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)piperazine-1-carboxylate, some clean tert-butyl 4-((5R,7S)-5-methyl-7-(4-nitrobenzoyloxy)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)piperazine-1-carboxylate and some mixed fractions were isolated. The mixed fractions were recolumned and combined with the previously isolated material to give tert-butyl 4-((5R,7R)-5-methyl-7-(4-nitrobenzoyloxy)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)piperazine-1-carboxylate (14.27 g, 38%) and tert-butyl 4-((5R,7S)-5-methyl-7-(4-nitrobenzoyloxy)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)piperazine-1-carboxylate (12.58 g, 34%). The use of 4-bromobenzoyl chloride has been shown to offer slightly better separation of the isomers.

후처리

  1. stirringstirred overnight (17 hours)
  2. stirringThe reaction mixture was stirred for 10 minutes
  3. customtransferred to a separatory funnel
  4. customThe organic layers were collected
  5. washthe aqueous extracts were washed with DCM (2×)
  6. dry with materialThe combined organic extracts were dried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated

출처 및 근거

ORD 기록
ord-16f9e9260c074a81afdcec4b5569e257
출처 데이터셋
uspto-grants-2014_09
특허 번호
US08835434B2

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