1-Hydroxybenzotriazole → [(R)-2-(3-fluoro-azetidin-1-yl)-1-methoxymethyl-2-oxo-ethyl]-carbamic acid tert-butyl ester

HRID 246167노트

반응식

HRID 246167 반응식
[C:1]([O:5][C:6]([NH:8][C@H:9]([CH2:13][O:14][CH3:15])[C:10]([OH:12])=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].Cl.[F:17][CH:18]1[CH2:21][NH:20][CH2:19]1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C1C=CC2N(O)N=NC=2C=1.C(N(CC)C(C)C)(C)C>CN(C=O)C>[C:1]([O:5][C:6](=[O:7])[NH:8][C@H:9]([CH2:13][O:14][CH3:15])[C:10]([N:20]1[CH2:21][CH:18]([F:17])[CH2:19]1)=[O:12])([CH3:2])([CH3:3])[CH3:4]

참가 물질

7

반응물 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 101250543-fluoroazetidine HydrochlorideHCID 27281801(2R)-2-{[(tert-butoxy)carbonyl]amino}-3-methoxypropanoic acid

생성물 1

HCID 71279849[(R)-2-(3-fluoro-azetidin-1-yl)-1-methoxymethyl-2-oxo-ethyl]-carbamic acid tert-butyl ester수율 53.1%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

실험 절차

A 25 mL round-bottomed flask was charged with (R)-2-tert-butoxycarbonylamino-3-methoxy-propionic acid (0.40 g, 1.82 mmol), 3-fluoroazetidine hydrochloride (204 mg, 1.82 mmol), HBTU (989 mg, 2.74 mmol), and HOBt (375 mg, 2.74 mmol). Then added DMF (3.6 mL) followed by N,N-diisopropylethylamine (1.27 mL, 7.3 mmol). The reaction mixture was stirred at room temperature overnight then quenched with water and extracted with EtOAc (30 mL). The organic layer was washed once with saturated NaHCO3 and water. The combined aqueous layers were back extracted with EtOAc (25 mL). The combined organic layers was dried over sodium sulfate, filtered and concentrated. The residue was purified by chromatography over SiO2 with EtOAc/heptane (gradient: 0-50% EtOAc) to afford 267 mg (53%) of [(R)-2-(3-fluoro-azetidin-1-yl)-1-methoxymethyl-2-oxo-ethyl]-carbamic acid tert-butyl ester as a white solid.

후처리

  1. customthen quenched with water
  2. extractionextracted with EtOAc (30 mL)
  3. washThe organic layer was washed once with saturated NaHCO3 and water
  4. extractionThe combined aqueous layers were back extracted with EtOAc (25 mL)
  5. dry with materialThe combined organic layers was dried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was purified by chromatography over SiO2 with EtOAc/heptane (gradient: 0-50% EtOAc)

출처 및 근거

ORD 기록
ord-92a6e1debc4d4e0a8746936267cb9775
출처 데이터셋
uspto-grants-2014_02
특허 번호
US08658646B2

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