[5-(3-Azido-phenyl)-5-fluoromethyl-5,6-dihydro-2H-[1,4]oxazin-3-yl]-carbamic acid tert-butyl ester → HCID 66665607, 화합물

HRID 81532

반응식

HRID 81532 반응식
[C:1]([O:5][C:6](=[O:25])[NH:7][C:8]1[CH2:9][O:10][CH2:11][C:12]([C:16]2[CH:21]=[CH:20][CH:19]=[C:18]([N:22]=[N+]=[N-])[CH:17]=2)([CH2:14][F:15])[N:13]=1)([CH3:4])([CH3:3])[CH3:2]>C1COCC1.CCO.[Pd]>[C:1]([O:5][C:6](=[O:25])[NH:7][C:8]1[CH2:9][O:10][CH2:11][C@:12]([C:16]2[CH:21]=[CH:20][CH:19]=[C:18]([NH2:22])[CH:17]=2)([CH2:14][F:15])[N:13]=1)([CH3:4])([CH3:2])[CH3:3]

참가 물질

5

반응물 1

HCID 86650252[5-(3-Azido-phenyl)-5-fluoromethyl-5,6-dihydro-2H-[1,4]oxazin-3-yl]-carbamic acid tert-butyl ester

생성물 1

HCID 66665607HCID 66665607, 화합물

시약·촉매·용매 3

HCID 23938Palladium촉매HCID 702Ethanol용매HCID 8028Tetrahydrofuran용매

실험 절차

A solution of 740 mg (2.118 mmol) [5-(3-azido-phenyl)-5-fluoromethyl-5,6-dihydro-2H-[1,4]oxazin-3-yl]-carbamic acid tert-butyl ester (Example 31h) in 5 ml THF and 5 ml EtOH was stirred in the presence of 35 mg 10% Pd—C under hydrogen. After 3 h the mixture was filtered over celite, concentrated and crystallized from EtOAc/hexane to give a beige solid. The racemic product was separated via prep HPLC on Chiralpak AD-H 250×4.6 mm column using heptan/EtOH 1:1 as an eluent. The desired compound was the slower eluting (R)-enantiomer. TLC: Rf (Hexane/EtOAc 2:1)=0.15. HPLC: RtH=1.764 min; ESIMS [M+H]+=324. 1H-NMR (CDCl3, 360 MHz, broad signals due to hindered rotation): 10.5 (br, 1H), 7.12 (br, 1H), 6.69 (d, 1H), 6.59 (br d, 1H), 4.8-4.0 (m, 8H), 1.48 (br s, 9H).

후처리

  1. filtrationAfter 3 h the mixture was filtered over celite,
  2. concentrationconcentrated
  3. customcrystallized from EtOAc/hexane
  4. customto give a beige solid
  5. customThe racemic product was separated via prep HPLC on Chiralpak AD-H 250×4.6 mm column
  6. washslower eluting (R)-enantiomer
  7. customRtH=1.764 min

출처 및 근거

ORD 기록
ord-9da3b1b7d6e046a3be9b62af4e12711d
출처 데이터셋
uspto-grants-2014_09
특허 번호
US08846658B2

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