Acetic Acid → tert-butyl {(5S)-3-[3-fluoro-4(4-morpholinyl)phenyl]-2-oxo-1,3-oxazolidin-5-yl}methylcarbamate

HRID 890636ノート

反応式

HRID 890636 の反応式
[C:1]1([CH2:7][O:8][C:9](=[O:24])[NH:10][C:11]2[CH:16]=[CH:15][C:14]([N:17]3[CH2:22][CH2:21][O:20][CH2:19][CH2:18]3)=[C:13]([F:23])[CH:12]=2)C=CC=CC=1.O1C[C@@H]1C[NH:29][C:30](=[O:36])[O:31][C:32]([CH3:35])([CH3:34])[CH3:33].[CH3:37]C(C)([O-])C.[Li+].C(O)(=O)C>C1COCC1.O.C(Cl)Cl>[F:23][C:13]1[CH:12]=[C:11]([N:10]2[CH2:37][C@H:7]([CH2:1][NH:29][C:30](=[O:36])[O:31][C:32]([CH3:35])([CH3:34])[CH3:33])[O:8][C:9]2=[O:24])[CH:16]=[CH:15][C:14]=1[N:17]1[CH2:18][CH2:19][O:20][CH2:21][CH2:22]1

参加物

8

反応物 4

HCID 176Acetic AcidHCID 5306150Carbamic acid, N-(3-fluoro-4-(4-morpholinyl)phenyl)-, phenylmethyl esterHCID 10080852(S)-N-Boc-2,3-epoxypropylamineHCID 236647642-Propanol, 2-methyl-, lithium salt (1:1)

生成物 1

HCID 11418025tert-butyl {(5S)-3-[3-fluoro-4(4-morpholinyl)phenyl]-2-oxo-1,3-oxazolidin-5-yl}methylcarbamate

試薬・触媒・溶媒 3

HCID 962Water溶媒HCID 6344Dichloromethane溶媒HCID 8028Tetrahydrofuran溶媒2 回

実験手順

To a slurry of [3-fluoro-4(4-morpholinyl)phenyl]carbamic acid phenylmethyl ester (Example 1) (1.0039 g, 3.039 mmol) and tert-butyl (2S)oxiranylmethylcarbamate (Example 5) (0.653 g, 3.77 mmol, 1.24 eq) in THF (1.5 ml) at 0° C. was added a solution of lithium t-butoxide in THF (18.07 wt %, 1.735 g, 3.92 mmol, 1.29 eq). After standing 2 days at 20–25° C., methylene chloride (5.0 ml), then acetic acid (0.35 ml, 6.11 mmol, 2.01 eq) followed by water (3.5 ml) was added. The phases were separated and the aqueous washed with methylene chloride (3.5 ml). The combined organics were dried on magnesium sulfate and concentrated to an oil which was shown to contain 1.03 g (85.7%) of Compound III, wherein R1=3-fluoro-4-(4-morpholinyl)phenyl, R3=t-butyl, by external standard HPLC: retention time=4.06 min (column=Zorbax SB-C8 3.5 micron 150×4.6 mm, flow rate=2.0 ml/min, gradient elution from 30:70 A:B to 90:10 A:B over 15 minutes; A=969:30:1 acetonitrile: THF: trifluoroacetic acid; B=949:50:1 water: THF:trifluroracetic acid).

後処理

  1. additionwas added
  2. customThe phases were separated
  3. washthe aqueous washed with methylene chloride (3.5 ml)
  4. customThe combined organics were dried on magnesium sulfate
  5. concentrationconcentrated to an oil which
  6. wash3.5 micron 150×4.6 mm, flow rate=2.0 ml/min, gradient elution from 30:70 A:B to 90:10 A:B over 15 minutes

出典と根拠

ORDレコード
ord-85c960d6e7694e318507a98af7a38236
出典データセット
uspto-grants-2006_02
特許番号
US06998420B2

反応ノート

読み込み中…