P-Toluic Acid → (3S,5S,6R)-6-Methyl-2-oxo-5-phenyl-1-(2,2,2-trifluoroethyl)piperidin-3-aminium 4-methylbenzoate

HRID 706368노트

반응식

HRID 706368 반응식
[CH3:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=[O:7])=[CH:4][CH:3]=1.[NH2:11][CH:12]1[CH2:17][C@@H:16]([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[C@@H:15]([CH3:24])[N:14]([CH2:25][C:26]([F:29])([F:28])[F:27])[C:13]1=[O:30]>CC(OC)(C)C.ClC1C=C(Cl)C=C(C=O)C=1O>[CH3:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([O-:8])=[O:7])=[CH:4][CH:3]=1.[CH3:24][C@H:15]1[N:14]([CH2:25][C:26]([F:29])([F:27])[F:28])[C:13](=[O:30])[C@@H:12]([NH3+:11])[CH2:17][C@H:16]1[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1

참가 물질

5

반응물 2

HCID 7470P-Toluic AcidHCID 89821829(5S,6R)-3-Amino-6-methyl-5-phenyl-1-(2,2,2-trifluoroethyl)piperidin-2-one

생성물 1

HCID 118023660(3S,5S,6R)-6-Methyl-2-oxo-5-phenyl-1-(2,2,2-trifluoroethyl)piperidin-3-aminium 4-methylbenzoate수율 86%

시약·촉매·용매 2

HCID 666603,5-Dichlorosalicylaldehyde촉매HCID 15413tert-Butyl methyl ether용매2회

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온도
50 °C

실험 절차

To a suspension of 4-methylbenzoic acid (6.8 g, 49.9 mmol) and 3,5-dichlorosalicylaldehyde (93 mg, 0.49 mmol) in MTBE (40 mL) was added a solution of 12 (13.9 g, 48.5 mmol) in MTBE (about 150 mL) over 1 h at 50° C. The resulting suspension was agitated for about 3 h at 50° C. The solids were collected by filtration after cooling to −5° C. over 1 h. The cake was washed with MTBE (50 mL). The solids were dried in a vacuum oven to give 13 (17.6 g, 86%) as crystals with 99.5% LC purity and 99.6% de. 1H NMR (DMSO-d6, 400 MHz): δ 7.85 (d, J=8.1 Hz, 2H), 7.40 (m, 2H), 7.25 (m, 5H), 6.0 (br, 3H), 4.65 (m, 1H), 3.65-3.80 (m, 2H), 3.45-3.65 (m, 2H), 2.35 (s, 3H), 2.30 (m, 1H), 2.15 (m, 1H), 0.88 (d, J=6.5 Hz, 3H); 13C NMR (DMSO-d6, 100 MHz): δ 172.4, 168.5, 142.1, 141.1, 130.9, 129.7, 129.2, 129.0, 128.0, 125.5 (q, J=279 Hz), 59.1, 51.6, 45.1 (q, J=32 Hz), 41.6, 28.0, 21.5, 13.9.

후처리

  1. filtrationThe solids were collected by filtration
  2. temperatureafter cooling to −5° C. over 1 h
  3. washThe cake was washed with MTBE (50 mL)
  4. customThe solids were dried in a vacuum oven

출처 및 근거

ORD 기록
ord-b3c1d244a8be4e7eb7d734d19948c24f
출처 데이터셋
uspto-grants-2015_11
특허 번호
US09174989B2

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