(S)-tert-Butyl (3-chloro-2-hydroxypropyl)carbamate → (-)-phenylmethyl 7-[(5S)-5-[[[(1,1-dimethylethoxy)carbonyl]amino]methyl]-2-oxo-3-oxazolidinyl]-3,4-dihydro-2(1H)-isoquinolinecarboxylate

HRID 488376노트

반응식

HRID 488376 반응식
C1(C[O:8][C:9]([NH:11][C:12]2[CH:21]=[C:20]3[C:15]([CH2:16][CH2:17][N:18]([C:22]([O:24][CH2:25][C:26]4[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=4)=[O:23])[CH2:19]3)=[CH:14][CH:13]=2)=O)C=CC=CC=1.Cl[CH2:33][C@@H:34]([OH:44])[CH2:35][NH:36][C:37](=[O:43])[O:38][C:39]([CH3:42])([CH3:41])[CH3:40].O(C(C)(C)C)[Li]>CN(C=O)C>[CH3:40][C:39]([CH3:42])([O:38][C:37]([NH:36][CH2:35][C@@H:34]1[O:44][C:9](=[O:8])[N:11]([C:12]2[CH:21]=[C:20]3[C:15]([CH2:16][CH2:17][N:18]([C:22]([O:24][CH2:25][C:26]4[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=4)=[O:23])[CH2:19]3)=[CH:14][CH:13]=2)[CH2:33]1)=[O:43])[CH3:41]

참가 물질

5

반응물 3

HCID 11195158(S)-tert-Butyl (3-chloro-2-hydroxypropyl)carbamateHCID 22269646phenylmethyl 3,4-dihydro-7-[[(phenylmethoxy)carbonyl]amino]-2(1H)-isoquinolinecarboxylateHCID 178506942HCID 178506942, 화합물

생성물 1

HCID 69734605(-)-phenylmethyl 7-[(5S)-5-[[[(1,1-dimethylethoxy)carbonyl]amino]methyl]-2-oxo-3-oxazolidinyl]-3,4-dihydro-2(1H)-isoquinolinecarboxylate수율 80%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

실험 절차

A solution of phenylmethyl 3,4-dihydro-7-[[(phenylmethoxy)carbonyl]amino]-2(1H)-isoquinolinecarboxylate (Step 3, 5.12 g, 12.29 mmol) and tert-butyl (2S)-3-chloro-2-hydroxypropylcarbamate (which can be prepared according to U.S. patent application, serial No. 60/241122, 3.22 g, 15.36 mmol) in dry DMF (5.6 mL) at 0° C. under N2 is treated with LiOtBu (1M in THF, 29.5 mL, 29.5 mmol) dropwise over 5 mins. The cooling bath is removed, and the resulting mixture is stirred at ambient temperature for 18 hrs, quenched with saturated aqueous NH4Cl (25 mL), diluted with H2O (25 mL) and extracted with EtOAc (50 mL). The EtOAc phase is then washed with H2O (2×50 mL) and brine (25 mL), dried over MgSO4 and concentrated under reduced pressure, and the residue is chromatographed on a Flash 40M silica gel (90 g, 32-63 μm) cartridge, eluting with a gradient of EtOAc/heptane (25/75-50/50). Those fractions with an Rf=0.20 by TLC (EtOAc/hexane, 50/50) are pooled and concentrated to give 4.69 g (80%) of the title compound as a white solid, mp 135-137° C. [α]25D=−27° (c 1.00, DMSO).

후처리

  1. customThe cooling bath is removed
  2. customquenched with saturated aqueous NH4Cl (25 mL)
  3. additiondiluted with H2O (25 mL)
  4. extractionextracted with EtOAc (50 mL)
  5. washThe EtOAc phase is then washed with H2O (2×50 mL) and brine (25 mL)
  6. dry with materialdried over MgSO4
  7. concentrationconcentrated under reduced pressure
  8. customthe residue is chromatographed on a Flash 40M silica gel (90 g, 32-63 μm) cartridge
  9. washeluting with a gradient of EtOAc/heptane (25/75-50/50)
  10. concentrationconcentrated

출처 및 근거

ORD 기록
ord-d1b37533946b42d0813109602b156558
출처 데이터셋
uspto-grants-2005_12
특허 번호
US06972286B2

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