Methanamine, N-methoxy-, hydrochloride (1:1) → (R)-[2-(4-Benzyloxy-phenyl)-1-(methoxy-methyl-carbamoyl)-ethyl]-carbamic acid tert-butyl ester

HRID 852865

反応式

HRID 852865 の反応式
CCN(C(C)C)C(C)C.[CH2:10]([O:17][C:18]1[CH:23]=[CH:22][C:21]([CH2:24][C@@H:25]([NH:29][C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31])[C:26](O)=[O:27])=[CH:20][CH:19]=1)[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1.F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.[CH3:64][O:65][NH:66][CH3:67].Cl>CN(C=O)C>[C:33]([O:32][C:30](=[O:31])[NH:29][C@@H:25]([C:26](=[O:27])[N:66]([O:65][CH3:64])[CH3:67])[CH2:24][C:21]1[CH:22]=[CH:23][C:18]([O:17][CH2:10][C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)=[CH:19][CH:20]=1)([CH3:35])([CH3:34])[CH3:36]

参加物

6

反応物 4

HCID 81138Methanamine, N-methoxy-, hydrochloride (1:1)HCID 81531DiisopropylethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 6992575Boc-D-Tyr(Bzl)-Oh

生成物 1

HCID 51356829(R)-[2-(4-Benzyloxy-phenyl)-1-(methoxy-methyl-carbamoyl)-ethyl]-carbamic acid tert-butyl ester

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒2 回

実験手順

DIPEA (28.2 ml, 20.9 g, 162 mmol) was added to a stirred solution of (R)-3-(4-benzyloxy-phenyl)-2-tert-butoxycarbonylamino-propionic acid (20.0 g, 53.9 mmol), BOP (25.00 g, 56.5 mmol) and MeONHMe.HCl (5.52 g, 56.6 mmol) in DMF (300 mL). After stirring 2 h the DMF was evaporated and the residue was dissolved in EtOAc and washed with water, 5% aqueous HCl, saturated aqueous NaHCO3 and brine, then dried with Na2SO4 and evaporated to a cream solid. This was ground to a powder (22.39 g, 100%), mp 107.1-108.7° C. (lit. mp 107-108° C.) [W. J. Thompson et al, Tetrahedron Lett, 1990, 31, 6189]. 1H NMR (CDCl3) δ 7.44-7.32 (5H, m), 7.09 (2H, d, J=8.5 Hz), 6.90 (2H, d, J=8.6 Hz), 5.15 (1H, br d, J=7.1 Hz, NH), 5.04 (2H, s, OCH2Ph), 4.91 (1H, br s, Hα), 3.17 (3H, s, NMe), 3.65 (3H, s, OMe), 3.00 (1H, dd, J=6.1, 13.6 Hz, Hβ), 2.83 (1H, dd, J=6.2, 14.2 Hz, Hβ), 1.40 (9H, s, CMe3). 13C NMR (CDCl3) δ 172.3, 157.7, 155.2, 137.1, 130.4, 128.9, 128.5, 127.9, 127.4, 114.7, 79.6, 70.0, 61.5, 51.6, 38.0, 32.1, 28.3.

後処理

  1. customwas evaporated
  2. dissolutionthe residue was dissolved in EtOAc
  3. washwashed with water, 5% aqueous HCl, saturated aqueous NaHCO3 and brine
  4. dry with materialdried with Na2SO4
  5. customevaporated to a cream solid

出典と根拠

ORDレコード
ord-ffb1b3dda9654865ab0d4f17e08b1e23
出典データセット
uspto-grants-2007_08
特許番号
US07253194B2

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