Triphenylphosphine → 2-Amino-5-fluoro-5-(2-methyl-4-nitro-pyrazol-3-yl)cycloheptanol

HRID 1915829노트

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HRID 1915829 반응식
[N:1]([CH:4]1[CH2:10][CH2:9][C:8]([F:20])([C:11]2[N:15]([CH3:16])[N:14]=[CH:13][C:12]=2[N+:17]([O-:19])=[O:18])[CH2:7][CH2:6][CH:5]1[OH:21])=[N+]=[N-].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>C1COCC1.O>[NH2:1][CH:4]1[CH2:10][CH2:9][C:8]([F:20])([C:11]2[N:15]([CH3:16])[N:14]=[CH:13][C:12]=2[N+:17]([O-:19])=[O:18])[CH2:7][CH2:6][CH:5]1[OH:21]

참가 물질

4

반응물 2

HCID 11776TriphenylphosphineHCID 866800222-azido-5-fluoro-5-(1-methyl-4-nitro-1H-pyrazol-5-yl)cycloheptanol

생성물 1

HCID 866800382-Amino-5-fluoro-5-(2-methyl-4-nitro-pyrazol-3-yl)cycloheptanol

시약·촉매·용매 1

HCID 21881883Oxolane--water (1/1)용매

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온도
60 °C

실험 절차

A solution of 2-azido-5-fluoro-5-(1-methyl-4-nitro-1H-pyrazol-5-yl)cycloheptanol (280 mg, 094 mmol) in THF/water (20 mL/4 mL) was treated with triphenylphosphine (270 g, 1.03 mmol) and the mixture was heated at 60° C. behind a blast screen for 18 hr. The solvents were removed under reduced pressure and the residue was purified via a SCX cartridge washing with MeOH and eluting with 3 N NH3 in MeOH to give 2-amino-5-fluoro-5-(2-methyl-4-nitro-pyrazol-3-yl)cycloheptanol as a colourless oil. To a solution of this oil (256 mg, 0.94 mmol) in dry DCM (20 mL) at 0° C. was added slowly DIPEA (0.49 mL, 2.82 mmol) followed by trifluoroacetic anhydride (0.16 ml, 1.13 mmol) dropwise. The reaction mixture was allowed to warm to room temperature and stirred for 18 hr. Water (20 mL) was added and the mixture was extracted with DCM (100 mL). The organic layer was passed through a phase separation cartridge and concentrated under reduced pressure. Purification via silica gel column chromatography (30-50% EtOAc/isohexane) gave 2,2,2-trifluoro-N-(5-fluoro-2-hydroxy-5-(2-methyl-4-nitro-pyrazol-3-yl)cycloheptyl)acetamide as a pale yellow oil (130 mg, 38% over two steps). 1H NMR (400 MHz, CDCl3) δ 8.07 and 8.06 (2s, 1H), 6.53 (s, 1H), 4.08 and 4.06 (2s, 3H), 4.05-3.92 (m, 2H), 3.06-2.69 (m, 3H), 2.32-1.89 (m, 6H).

후처리

  1. customThe solvents were removed under reduced pressure
  2. customthe residue was purified via a SCX cartridge
  3. washwashing with MeOH
  4. washeluting with 3 N NH3 in MeOH

출처 및 근거

ORD 기록
ord-a1eadc431a7240cd91fe679e7938e4a3
출처 데이터셋
uspto-grants-2013_12
특허 번호
US08614206B2

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