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

HRID 532512ノート

反応式

HRID 532512 の反応式
C(N(CC)CC)C.[CH3:8][C@H:9]1[C:17]2[C:16]([N:18]3[CH2:23][CH2:22][N:21]([C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[CH2:20][CH2:19]3)=[N:15][CH:14]=[N:13][C:12]=2[C:11](=[O:31])[CH2:10]1.O[C@H]1C2N=CN=C(N3CCN(C(OC(C)(C)C)=O)CC3)C=2[C@H](C)C1>C(Cl)Cl>[OH:31][C@@H:11]1[C:12]2[N:13]=[CH:14][N:15]=[C:16]([N:18]3[CH2:23][CH2:22][N:21]([C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[CH2:20][CH2:19]3)[C:17]=2[C@H:9]([CH3:8])[CH2:10]1

参加物

5

反応物 3

HCID 8471TriethylamineHCID 59580343tert-butyl 4-((5R,7R)-7-hydroxy-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)piperazine-1-carboxylateHCID 59580350(R)-tert-butyl 4-(5-methyl-7-oxo-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)piperazine-1-carboxylate

生成物 1

HCID 59580357tert-Butyl 4-((5R,7S)-7-hydroxy-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)piperazine-1-carboxylate収率 95.4%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

Triethylamine (4.33 mL, 31.1 mmol; degassed with nitrogen 30 minutes prior to use) and formic acid (1.36 mL, 36.1 mmol; degassed with nitrogen 30 minutes prior to use) were added to a solution of (R)-tert-butyl 4-(5-methyl-7-oxo-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)piperazine-1-carboxylate (9.75 g, 29.3 mmol) in DCM (210 mL; degassed with nitrogen 30 minutes prior to use). The mixture was stirred for 5 minutes, and then a Ru catalyst (0.0933 g, 0.147 mmol) was added. The reaction was stirred under positive nitrogen pressure overnight (18 hours). The reaction mixture was concentrated to dryness and dried on high vacuum. The impure material was flashed on Biotage 65M loaded 1:1 DCM:ethyl acetate 500 mL flushed, then 1:4 DCM:ethyl acetate until product (2nd spot), then gradient to neat ethyl acetate, then 25:1 DCM:MeOH eluted rest of product. The fractions were combined and concentrated on a rotary evaporator. The residue was concentrated again from DCM/hexanes to give a mixture of tert-butyl 4-((5R,7R)-7-hydroxy-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)piperazine-1-carboxylate (major) and tert-butyl 4-((5R,7S)-7-hydroxy-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)piperazine-1-carboxylate (minor) (9.35 g, 95.3% yield) as a foam. LC/MS (APCI+) m/z 335 [M+H]+. 1H NMR (CDCl3) showed 88% diastereoselectivity by integration of carbinol methine.

後処理

  1. customdegassed with nitrogen 30 minutes
  2. customdegassed with nitrogen 30 minutes
  3. customdegassed with nitrogen 30 minutes
  4. stirringThe reaction was stirred under positive nitrogen pressure overnight (18 hours)
  5. concentrationThe reaction mixture was concentrated to dryness
  6. customdried on high vacuum
  7. customethyl acetate 500 mL flushed
  8. concentrationconcentrated on a rotary evaporator
  9. concentrationThe residue was concentrated again from DCM/hexanes
  10. customto give

出典と根拠

ORDレコード
ord-d1acdc60ea5d4ed0a6cd226a42a32284
出典データセット
uspto-grants-2014_10
特許番号
US08853216B2

反応ノート

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