Isopropyl Acetate → 2-Amino-1,2-diphenylethanol

HRID 132759노트

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HRID 132759 반응식
[Br:1][CH:2]([CH2:6][CH2:7][N:8]1[C:12](=[O:13])[C:11]([CH3:15])([CH3:14])[N:10]([CH3:16])[C:9]1=[O:17])[C:3]([OH:5])=[O:4].[NH2:18][C@@H:19]([C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1)[C@@H:20]([C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)[OH:21].C(OC(C)C)(=O)C>[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.C(OC)(C)(C)C>[Br:1][C@H:2]([CH2:6][CH2:7][N:8]1[C:12](=[O:13])[C:11]([CH3:15])([CH3:14])[N:10]([CH3:16])[C:9]1=[O:17])[C:3]([OH:5])=[O:4].[NH2:18][CH:19]([C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1)[CH:20]([C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)[OH:21]

참가 물질

7

반응물 3

HCID 7915Isopropyl AcetateHCID 719819(1R,2S)-2-Amino-1,2-diphenylethanolHCID 11324242HCID 11324242, 화합물

생성물 2

HCID 222432-Amino-1,2-diphenylethanolHCID 11168359HCID 11168359, 화합물

시약·촉매·용매 2

HCID 74236Tetrabutylammonium Bromide촉매HCID 15413tert-Butyl methyl ether용매

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온도
57.5 °C

실험 절차

α-Bromo-3,4,4-trimethyl-2,5-dioxo-1-imidazolidinebutanoic acid (I) (111 g, 362.4 mmol) and (1R,2S)-(−)-2-amino-1,2-diphenylethanol (II) (the chiral amine, 75 g, 351 mmol, Aldrich) and tetrabutylammonium bromide (catalytic nucleophile, 2.4 g) were charged to a flask. I was obtained by/from Aerojet Fine Chemicals (a Division of Gencorp, Rancho Cordova, Calif.). To this was added 3 L of a 1:1 mixture of i-propyl acetate (i-PrOAc) and methyl t-butyl ether (MTBE). The resulting slurry was heated to 55-60° C. for 24 to 48 h. Reaction was deemed complete when the ratio of the diastereomers was ≧94:6 (R:S). The reaction was cooled to room temperature and the diastereomeric salt, (R)-α-bromo-3,4,4-trimethyl-2,5-dioxo-1-imidazolidinebutanoic acid, [R-(R*,S*)]-β-amino-α-phenylbenzeneethanol salt (1:1) (IA), was isolated by filtration. The product cake was washed with 850 mL of MTBE. The MTBE wet product cake was suspended in 1800 mL of MTBE. Water, 1800 mL was added. The pH of the aqueous phase was adjusted to between 1 and 2 with methanesulfonic acid (˜23 mL). The phases were separated and the lower aqueous phase was extracted with MTBE (3×1L). The combined organic phases were washed with water (250 mL). The product, (R)-α-bromo-3,4,4-trimethyl-2,5-dioxo-1-imidazolidinebutanoic acid (IB)was used directly in the next step without isolation. In process yield and quality was 101.0 g, 93.0 M%, 87.4% ee (enantiomeric excess). IB: 1H NMR (CDCl3): δ(ppm)=4.30 (m, 1H), 3.72 (m, 2H), 2.96 (s, 3 H), 2.48 (m, 1H), 2.27 (m, 1H), 1.39 (s, 6H). 13C NMR (CDCl3): δ (ppm)=176.7, 172.2, 155.2, 61.4, 41.7, 36.6, 33.2, 24.4, 21.9, 21.9. IR (KBr): ν (cm−1)=3000 (br), 1740 (s), 1680 (s), 1450 (br), 1250 (s).

후처리

  1. additionTo this was added
  2. customReaction
  3. temperatureThe reaction was cooled to room temperature

출처 및 근거

ORD 기록
ord-02bdcb72c95742708d81979c4a6c7a51
출처 데이터셋
uspto-grants-2008_06
특허 번호
US07388098B2

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