Isopropanol → 1-benzyl-1'-isopropyl-1'H-spiro[piperidine-4,5'-pyrano[3,2-c]pyrazol]-7'(6'H)-one

HRID 2284355

反応式

HRID 2284355 の反応式
[CH2:1]([N:8]1[CH2:22][CH2:21][C:11]2([O:19][C:18]3[CH:17]=[N:16][NH:15][C:14]=3[C:13](=[O:20])[CH2:12]2)[CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:23][CH:24](O)[CH3:25].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1C=CC(COC(/N=N/C(OCC2C=CC=CC=2)=O)=O)=CC=1>O1CCCC1>[CH2:1]([N:8]1[CH2:22][CH2:21][C:11]2([O:19][C:18]3[CH:17]=[N:16][N:15]([CH:24]([CH3:25])[CH3:23])[C:14]=3[C:13](=[O:20])[CH2:12]2)[CH2:10][CH2:9]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

参加物

6

反応物 4

HCID 3776IsopropanolHCID 11776TriphenylphosphineHCID 5387121Dibenzyl azodicarboxylateHCID 680654501-benzyl-1'H-spiro[piperidine-4,5'-pyrano[3,2-c]pyrazol]-7'(6'H)-one

生成物 1

HCID 680661841-benzyl-1'-isopropyl-1'H-spiro[piperidine-4,5'-pyrano[3,2-c]pyrazol]-7'(6'H)-one収率 39.6%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

実験手順

1-Benzyl-1′H-spiro[piperidine-4,5′-pyrano[3,2-c]pyrazol]-7′(6′H)-one (204 mg, 0.67 mmol) was dissolved in 10 mL tetrahydrofuran. 2-propanol (0.11 mL, 1.37 mmol) and polymer supported triphenylphosphine (0.5 g, 3 mmol/g loading) were added followed by addition of DBAD (322 mg, 1.37 mmol) and stirred at ambient temperature for 5 days. Filtered off polymer supported triphenyl phosphine and washed filtercake with 100 mL ethyl acetate. The filtrate was concentrated and the resultant yellow oil was treated with 10 mL 4N HCl/dioxane. The mixture was stirred 1 h at ambient temperature. The volatiles were removed under reduced pressure. The resultant sludge was partitioned between 50 mL sat aq. sodium bicarbonate and 50 mL ethyl acetate. The organic phase was dried over sodium sulfate, filtered and concentrated under reduced pressure. The resultant oil was flash chromatographed (30-100% ethyl acetate/heptane gradient, 10 g silica) to yield 90 mg (35%) of 1-benzyl-1′-isopropyl-1′H-spiro[piperidine-4,5′-pyrano[3,2-c]pyrazol]-7′(6′H)-one as a pale yellow solid. 1H NMR (400 MHz, CDCl3) δ ppm 7.30 (m, 3H), 7.24 (m, 2H), 7.18 (s, 1H), 5.14 (spt, 1H), 3.52 (s, 2H), 2.60 (m, 4H), 2.41 (td, J=11.6, 2.5 Hz, 2H), 2.06 (d, J=12.5 Hz, 2H), 1.71 (m, 2H), 1.44 (m, 6H): m/z (M+1)=340.5.

後処理

  1. additionwere added
  2. filtrationFiltered off polymer
  3. washwashed filtercake with 100 mL ethyl acetate
  4. concentrationThe filtrate was concentrated
  5. additionthe resultant yellow oil was treated with 10 mL 4N HCl/dioxane
  6. stirringThe mixture was stirred 1 h at ambient temperature
  7. customThe volatiles were removed under reduced pressure
  8. customThe resultant sludge was partitioned between 50 mL
  9. dry with materialThe organic phase was dried over sodium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated under reduced pressure
  12. customchromatographed (30-100% ethyl acetate/heptane gradient, 10 g silica)

出典と根拠

ORDレコード
ord-05081d5d74b1431aa016264d7e10f9bd
出典データセット
uspto-grants-2015_09
特許番号
US09145416B2

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