Hydrochloric Acid → HCID 71562243, 화합물

HRID 1253412노트

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HRID 1253412 반응식
CON(C)[C:4](=O)[C@@H:5]([NH:22][C:23]([C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1)([C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1)[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1)[CH2:6][C:7]1[CH:21]=[CH:20][C:10]([CH2:11][NH:12][C:13](=[O:19])[O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[CH:9][CH:8]=1.[H-].[H-].[H-].[H-].[Li+].[Al+3].Cl.[CH3:51][S:52]([CH2:55]P(=O)(OCC)OCC)(=[O:54])=[O:53].[H-].[Na+]>CCOCC.C1COCC1.CCOC(C)=O>[CH3:51][S:52](/[CH:55]=[CH:4]/[C@@H:5]([NH:22][C:23]([C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1)([C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1)[C:30]1[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=1)[CH2:6][C:7]1[CH:21]=[CH:20][C:10]([CH2:11][NH:12][C:13](=[O:19])[O:14][C:15]([CH3:16])([CH3:18])[CH3:17])=[CH:9][CH:8]=1)(=[O:53])=[O:54]

참가 물질

9

반응물 5

HCID 313Hydrochloric AcidHCID 24758Sodium hydrideHCID 533797Diethyl (methanesulfonylmethyl)phosphonateHCID 21226445Aluminium lithium hydrideHCID 71562242(S)-tert-butyl 4-(3-(methoxy(methyl)amino)-3-oxo-2-(tritylamino)propyl)benzylcarbamate

생성물 1

HCID 71562243HCID 71562243, 화합물

시약·촉매·용매 3

HCID 3283Diethyl Ether용매2회HCID 8028Tetrahydrofuran용매HCID 8857Ethyl Acetate용매2회

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온도
0 °C

실험 절차

Weinreb amide 16 (0.65 g, 1.12 mmol) was dissolved in Et2O (15 mL), put under an argon atmosphere and cooled to 0° C. LiAlH4 (2 eq., 2.25 mmol, 0.56 mL of a 4 M solution in Et2O) was added slowly and the mixture was stirred at 0° C. for 1 hour after which TLC analysis indicated complete conversion of the starting compound. 0.1 M aq. HCl (15 mL) was slowly added and the layers were separated. The organic layer was extracted with 0.1 M aq. HCl and brine, dried over MgSO4 and concentrated under reduced pressure. Diethyl ((methylsulfonyl)methyl)phosphonate (1.5 eq., 1.68 mmol, 0.39 g) was dissolved in THF (20 mL) and cooled to 0° C. under an argon atmosphere. NaH (1.5 eq., 1.68 mmol, 67.2 mg, 60% w/w in mineral oil) was slowly added and the mixture was stirred at 0° C. for 30 minutes. Next, the freshly obtained aldehyde (in THF (2 mL)) was slowly added and the mixture was stirred for 2 hours while slowly warming it to room temperature. After this time TLC analysis indicated complete conversion of the aldehyde. EtOAc (20 mL) was added and the mixture was extracted with mM aq. HCl (2×) and brine, dried over MgSO4 and concentrated under reduced pressure. The title compound was obtained after column chromatography (20%→50% EtOAc/PE) as a colourless foam (yield: 0.57 g, 0.95 mmol, 85%). 1H NMR (400 MHz, CDCl3): δ=7.46 (d, J=7.6 Hz, 6H), 7.28 (t, J=7.20, 6.80 Hz, 6H), 7.20 (t, J=7.20, 7.20 Hz, 3H), 7.13 (d, J=7.60 Hz, 2H), 6.87 (d, J=8.00 Hz, 2H), 6.57 (dd, J=14.80, 7.00 Hz, 1H), 5.96 (d, J=14.80 Hz, 1H), 4.80 (s, 1H), 4.24 (d, J=5.60 Hz, 2H), 3.49 (q, J=6.00 Hz, 1H), 2.61 (s, 3H), 2.54 (dd, J=13.20, 5.20 Hz, 1H), 2.33 (dd, J=13.20, 8.20 Hz, 1H), 1.44 (s, 9H) ppm. 13C NMR (100 MHz, CDCl3): δ=155.59, 150.21, 145.74, 137.42, 135.28, 129.53, 128.35, 128.02, 127.70, 127.14, 126.44, 78.91, 71.05, 55.33, 43.79, 42.43, 41.86, 28.09 ppm. [α]D≦=−21.3 (c=1, CHCl3). HRMS: calcd. for C36H40N2O4S 619.26010 [M+Na]+. Found 619.26001.

후처리

  1. customthe layers were separated
  2. extractionThe organic layer was extracted with 0.1 M aq. HCl and brine
  3. dry with materialdried over MgSO4
  4. concentrationconcentrated under reduced pressure
  5. temperaturecooled to 0° C. under an argon atmosphere
  6. stirringthe mixture was stirred at 0° C. for 30 minutes
  7. stirringthe mixture was stirred for 2 hours
  8. temperaturewhile slowly warming it to room temperature
  9. extractionthe mixture was extracted with mM aq. HCl (2×) and brine
  10. dry with materialdried over MgSO4
  11. concentrationconcentrated under reduced pressure

출처 및 근거

ORD 기록
ord-74d88ecdba7d43c7ba5b8b3c9b44cdfb
출처 데이터셋
uspto-grants-2013_06
특허 번호
US08455431B2

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