(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 488376ノート

反応式

HRID 488376 の反応式
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]

参加物

5

反応物 3

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

生成物 1

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

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

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).

後処理

  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

出典と根拠

ORDレコード
ord-d1b37533946b42d0813109602b156558
出典データセット
uspto-grants-2005_12
特許番号
US06972286B2

反応ノート

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