Acetic Acid → Methyl(1R,2R,5S,6S)-2-{[tert-butyl(dimethyl)silyl]oxy}-6-fluoro-4-oxobicyclo[3.1.0]hexane-6-carboxylate

HRID 507819노트

반응식

HRID 507819 반응식
[CH3:1][O:2][C:3]([C@:5]1([F:20])[C@@H:10]2[C@H:6]1[C@@H:7]([OH:19])[CH2:8][C@H:9]2[O:11][Si:12]([C:15]([CH3:18])([CH3:17])[CH3:16])([CH3:14])[CH3:13])=[O:4].C(O)(=O)C.O.Cl[O-].[Na+]>C(#N)C.CO.CC(OC)(C)C.CCCCCC.C(O)(C)C>[Si:12]([O:11][C@@H:9]1[CH2:8][C:7](=[O:19])[C@@H:6]2[C@H:10]1[C@@:5]2([F:20])[C:3]([O:2][CH3:1])=[O:4])([C:15]([CH3:18])([CH3:17])[CH3:16])([CH3:14])[CH3:13]

참가 물질

9

반응물 4

HCID 176Acetic AcidHCID 962WaterHCID 11681051Methyl(1R,2R,4S,5S,6R)-2-{[tert-butyl(dimethyl)silyl]oxy}-6-fluoro-4-hydroxybicyclo[3.1.0]hexane-6-carboxylate2회HCID 23665760Sodium Hypochlorite2회

생성물 1

HCID 11587530Methyl(1R,2R,5S,6S)-2-{[tert-butyl(dimethyl)silyl]oxy}-6-fluoro-4-oxobicyclo[3.1.0]hexane-6-carboxylate

시약·촉매·용매 4

HCID 887Methanol용매HCID 3776Isopropanol용매HCID 6342Acetonitrile용매HCID 21982663Methyl t-butylether hexane용매

실험 절차

To a solution of bicyclic mono-TBS-diol 5 (2.08 kg; 6.83 mol) in acetonitrile (8.0 L) at −5° C. was added acetic acid (0.70 L) and water (2.5 L), followed by RuCl3 hydrate (14.20 g). To the mixture was added aqueous sodium hypochlorite solution (˜13%; 7.0 L) over 2 h, keeping the temperature around 0° C. The resulting mixture was stirred at 0° C. for another 1 h until all bicyclic mono-TBS-diol 5 disappeared, monitoring by TLC and NMR. The excess aqueous sodium hypochlorite was decomposed by the addition of isopropanol (0.70 L), aged at 0° C. for 15 min. The two layers were cut and the aqueous layer was discarded. The solution was used for the next reaction without further treatment. Analytical pure sample was obtained by flash silica gel column chromatography (MTBE/hexane) as colorless crystals: mp 70-71° C.; 1H NMR (400 MHz, CDCl3): δ 4.66 (d, J=5.4 Hz, 1H), 3.86 (s, 3H), 3.73 (s, 3H), 2.73 (m, 2H), 2.54 (dt, J=19.1, 5.7 Hz, 1H), 2.22 (dd, J=19.1, 3.8 Hz, 1H), 0.91 (s, 9H), 0.13 (s, 3H), 0.11 (s, 3H); 13C NMR (101 MHz, CDCl3): δ 206.2, 167.1 (d, J=26.1 Hz), 78.9 (d, J=246.4 Hz), 67.6 (d, J=2.8 Hz), 53.4, 47.5 (d, J=3.9 Hz), 42.0 (d, J=11.4 Hz), 39.6 (d, J=13.3 Hz), 25.7, 18.0, −4.76, and −4.78; 19F NMR (376 MHz, CDCl3): δ −210.7; [α]D25=+58.2 (c 0.50, CH3OH).

후처리

  1. customthe temperature around 0° C
  2. customThe solution was used for the next reaction without further treatment

출처 및 근거

ORD 기록
ord-4c11e9fd1d0d46199a0439796820885d
출처 데이터셋
uspto-grants-2010_08
특허 번호
US07786314B2

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