(2S,4R)-1-allyloxycarbonyl-4-hydroxy-2-hydroxymethylpyrrolidine → (11aS)-7-Iodo-2-methylidene-1,2,3,11a-tetrahydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-5-one

HRID 915702Notes

Reaction equation

HRID 915702 reaction equation
C(OC(N1C[C@H](O)C[C@H]1CO[Si](C(C)(C)C)(C)C)=O)C=C.C(OC(N1C[C@H](O)C[C@H]1CO)=O)C=C.O[C@H:37]1[C@@H:43]2[CH2:44][C:45](=[CH2:47])[CH2:46][N:42]2[C:41](=[O:48])[C:40]2[CH:49]=[C:50]([I:53])[CH:51]=[CH:52][C:39]=2[N:38]1NC(OCC(Cl)(Cl)Cl)=O.[Si](OC[C@@H]1CC(=C)CN1)(C(C)(C)C)(C)C>>[I:53][C:50]1[CH:51]=[CH:52][C:39]2[N:38]=[CH:37][C@@H:43]3[CH2:44][C:45](=[CH2:47])[CH2:46][N:42]3[C:41](=[O:48])[C:40]=2[CH:49]=1

Participants

5

Reactant 4

HCID 15086219(2S,4R)-1-allyloxycarbonyl-4-hydroxy-2-hydroxymethylpyrrolidine8×HCID 18639173(2S,4R)-1-allyloxycarbonyl-2-t-butyldimethylsilyloxymethyl-4-hydroxypyrrolidine6×HCID 58400350(2S)-2-[[[(1,1-Dimethylethyl)dimethylsilyl]oxy]methyl]-4-methylenepyrrolidine2×HCID 69462904(11S,11aS)-11-Hydroxy-7-iodo-2-methylidene-10-(2,2,2-trichloroethyloxycarbonylamino)-1,2,3,10,11,11a-hexahydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-5-one

Product 1

HCID 9862665(11aS)-7-Iodo-2-methylidene-1,2,3,11a-tetrahydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-5-one

Procedure

10% cadmium-lead couple (109 mg, 0.875 mmol) was added to a stirred solution of the Troc-protected carbinolamine 13 (93 mg, 0.175 mmol) in THF (1 mL) and aqueous 1 N ammonium acetate (1 mL). After 45 minutes at room temperature TLC revealed complete reaction (70% EtOAc/Petroleum Ether). The mixture was diluted with EtOAc (30 mL), dried (MgSO4), filtered and evaporated in vacuo. The crude residue was purified by flash chromatography (70% EtOAc/Petroleum Ether) to provide the novel PBD (14, BSD-SJG, UP2023) as a white solid (27 mg, 46%): mp ° C.; 1H NMR (270 MHz, CDCl3+CD3OD) (11S,11aS isomer) δ 8.10 (d, 1H, J=1.46Hz), 7.65 (d, 1H, J=8.79 Hz), 6.86 (d, 1H, J=8.06 Hz), 5.14-5.10 (m, 2H), 4.66 (d, 1H, J=5.13 Hz), 4.34 (d, 1H, J=16.12 Hz), 4.23 (d, 1H, J=16.12 Hz), 3.80-3.71 (m, 1H), 3.34 (s, 3H), 3.03-2.86 (m, 1H), 2.65 (d, 1H, J=16.02 Hz); MS (EI), m/z (relative intensity) (N10-C11 imine form) 339 (M++1, 20), 338 (M+, 100), 337 (17), 323 (5), 311 (4), 310 (5), 257 (5), 230 (4), 229 (13), 211 (4), 203 (4), 202 (8), 184 (8), 183 (4), 103 (5), 82 (17), 81 (4), 80 (5), 76 (6), 75 (16), 74 (5), 55 (4), 53 (4); IR (NUJOL7) 3295 (br), 2923, 2853, 1716, 1615, 1506, 1457, 1377, 1317, 1278, 1238, 1169, 1118, 1063, 999, 895, 818, 751, 718 cm−1; exact mass calcd for C13H11N2OI m/e 337.9916, obsd m/e 337.9870.

Sources & evidence

ORD record
ord-3e4596c16c254c0d9b06844ed508f540
Source dataset
uspto-grants-2007_09
Patent number
US07265105B2

Reaction notes

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