Hydrochloric Acid → Benzyl N-[(3R)-2-oxo-1,3,4,5-tetrahydro-1-benzazepin-3-yl]carbamate

HRID 2068528ノート

反応式

HRID 2068528 の反応式
Cl.[O:2]=[C:3]1[C@H:9]([NH:10][C:11](=[O:17])[O:12][C:13]([CH3:16])(C)C)[CH2:8][CH2:7][C:6]2[CH:18]=[CH:19][CH:20]=[CH:21][C:5]=2[NH:4]1.N[C@@H]1C[CH2:28][C:27]2C=C[CH:32]=[CH:33][C:26]=2NC1=O.C(=O)([O-])[O-].[Na+].[Na+].ClC(OCC1C=CC=CC=1)=O>O.C(OCC)(=O)C.C(#N)C.CO>[O:2]=[C:3]1[C@H:9]([NH:10][C:11](=[O:17])[O:12][CH2:13][C:16]2[CH:32]=[CH:33][CH:26]=[CH:27][CH:28]=2)[CH2:8][CH2:7][C:6]2[CH:18]=[CH:19][CH:20]=[CH:21][C:5]=2[NH:4]1

参加物

10

反応物 5

HCID 313Hydrochloric AcidHCID 10340Sodium CarbonateHCID 10387Benzyl chloroformateHCID 10103689(R)-3-amino-4,5-dihydro-1H-benzo[b]azepin-2(3H)-oneHCID 10923829(R)-(2-Oxo-2,3,4,5-tetrahydro-1H-benzo[b]azepin-3-yl)-carbamic acid tert-butyl ester

生成物 1

HCID 58304068Benzyl N-[(3R)-2-oxo-1,3,4,5-tetrahydro-1-benzazepin-3-yl]carbamate収率 105%

試薬・触媒・溶媒 4

HCID 887Methanol溶媒HCID 962Water溶媒HCID 6342Acetonitrile溶媒HCID 8857Ethyl Acetate溶媒

実験手順

Combine methanol (5000 mL) and 5N aqueous hydrogen chloride solution (1393 mL, 5.57 mol) and heat to 35° C. for 15 minutes. Add tert-butyl N-[(3R)-2-oxo-1,3,4,5-tetrahydro-1-benzazepin-3-yl]carbamate (Armstrong III, Joseph D, et al, Tetrahedron Let. 35(20) pp. 3239-3242 (1994) (770 g, mmol and commercially available) portionwise over 1 hour. Concentrate the mixture under reduced pressure to a white solid. Combine this solid with additional (3R)-3-amino-1,3,4,5-tetrahydro-1-benzazepin-2-one (different lot, same method; 660 g, 3.78 mol) and dissolve in water (2.5 L). To the resulting solution add sodium carbonate (3.17 kg, 3.18 mol) and acetonitrile (7.5 L). Add benzyl chloroformate (7.14 mol, 1.21 Kg) dropwise over 2 hours. After 2 hours at ambient temperature, add ethyl acetate (8 L) and filter. Wash the wet cake with water (4.0 L), acetonitrile (2.0 L), and ethyl acetate (3.0 L). Dry the solid under reduced pressure for 48 hours to give the title compound (2.14 kg, 105%): MS (m/z): 310.8 (M+1).

後処理

  1. concentrationConcentrate the mixture under reduced pressure to a white solid
  2. waitAfter 2 hours at ambient temperature
  3. filtrationfilter
  4. washWash the wet cake with water (4.0 L), acetonitrile (2.0 L), and ethyl acetate (3.0 L)
  5. customDry the solid under reduced pressure for 48 hours

出典と根拠

ORDレコード
ord-285664f0717846739a2f66066f24dc97
出典データセット
uspto-grants-2012_10
特許番号
US08299061B2

反応ノート

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