(2S,4R)-1-allyloxycarbonyl-2-methoxycarbonyl-4-hydroxypyrrolidine → (11aS)-8-Benzyloxy-7-methoxy-2-methylidene-1,2,3,11a-tetrahydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-5-one

HRID 915705Notes

Reaction equation

HRID 915705 reaction equation
C(OC(N1[CH2:11][C@H:10](O)[CH2:9][C@H:8]1[C:13]([O:15]C)=O)=O)C=C.[CH2:17]([O:20]C(N1C[C@H](O)C[C@H]1CO[Si](C(C)(C)C)(C)C)=O)C=C.[NH2:38][C:39]1[CH:54]=[CH:53][C:52](I)=[CH:51][C:40]=1[C:41]([N:43]1[CH2:47][C:46](=[CH2:48])[CH2:45][C@H:44]1[CH2:49]O)=[O:42].[CH2:56](OC(N1C[C@H](O)C[C@H]1CO)=O)[CH:57]=C>C(Cl)(Cl)Cl>[CH2:13]([O:15][C:53]1[C:52]([O:20][CH3:17])=[CH:51][C:40]2[C:41](=[O:42])[N:43]3[CH2:47][C:46](=[CH2:48])[CH2:45][C@H:44]3[CH:49]=[N:38][C:39]=2[CH:54]=1)[C:8]1[CH:9]=[CH:10][CH:11]=[CH:57][CH:56]=1

Participants

6

Reactant 4

HCID 10633157(2S,4R)-1-allyloxycarbonyl-2-methoxycarbonyl-4-hydroxypyrrolidineHCID 15086219(2S,4R)-1-allyloxycarbonyl-4-hydroxy-2-hydroxymethylpyrrolidine2×HCID 18639173(2S,4R)-1-allyloxycarbonyl-2-t-butyldimethylsilyloxymethyl-4-hydroxypyrrolidine3×HCID 69463669(2S)-N-(2-Amino-5-iodobenzoyl)-2-(hydroxymethyl)-4-methylidenepyrrolidine2×

Product 1

HCID 9884692(11aS)-8-Benzyloxy-7-methoxy-2-methylidene-1,2,3,11a-tetrahydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-5-one

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent

Procedure

A catalytic amount of tetrakis(triphenylphosphine)palladium (12.0 mg, 10.4 μmol) was added to a stirred solution of the Alloc-protected carbinolamine 20 (0.18 g, 0.40 mmol), triphenylphosphine (5.25 mg, 20 μmol) and pyrrolidine (29 mg, 0.41 mmol) in CH2Cl2 (15 mL). After 2 hours stirring at room temperature under a nitrogen atmosphere, TLC (98% CHCl3/MeOH) revealed the complete consumption of starting material. The solvent was evaporated in vacuo and the crude residue was purified by flash chromatography (60% EtOAc/Petroleum Ether) to afford 21 (SJG-244) as a white glass (116 mg, 83%) which was repeatedly evaporated in vacuo with CHCl3 in an attempt to provide the N10-C11 imine form: [α]22D=+754.2° (c=0.54, CHCl3); 1H NMR (270 MHz, CDCl3) (mainly imine, plus trace of carbinolamine form) δ 7.70-7.30 (m, 7H, HCαN and 6Harom), 6.84 (s, 1Harom), 5.25-5.13 (m, 4H, NCH2C═CH2 and PhCH2O), 4.42 (br s, 2H, NCH2C═CH2), 3.95 (s, 3H, OCH3), 3.88-3.66 (m, 1H, NCHHC═N), 3.09 (dd, 1H, J=8.98, 16.12 Hz, NCH2C═CH2CH2), 2.94-2.87 (m, 1H, NCH2C═CH2CH2); 13C NMR (67.8 MHz, CDCl3) δ 164.7 (NC═O), 162.6 (HC═N), 150.6 (Cquat), 148.1 (Cquat), 141.6 (Cquat), 140.5 (Cquat), 136.1 (Cquat), 132.0, 128.7, 128.6, 128.1 and 127.3 (BnC—Harom), 120.1 (Cquat), 111.5 (C—Harom), 111.2 (C—Harom), 109.4 (NCH2C═CH2), 70.8 (PhCH2O), 56.2 (OCH3), 53.7 (NCHHC═N), 51.3 (NCH2C═CH2), 35.4 (NCH2C═CH2CH2); MS (EI), m/z (relative intensity) (imine form) 348 (M+, 100), 333 (M-CH3, 42), 319 (3), 269 (5), 257 (M-PhCH2, 25), 241 (11), 229 (56), 227 (11), 213 (5), 186 (4), 156 (6), 136 (22), 122 (4), 91 (PhCH2, 85), 82 (5), 65 (22); IR (NUJOL7) 3318 (br, OH of carbinolamine form), 2923, 2853, 1722, 1668, 1600, 1557, 1504, 1462, 1377, 1261, 1216, 1120, 1003, 892, 789, 722, 695, 623, 542 cm−1; exact mass calcd for C21H20N2O3m/e 348.1474, obsd m/e 348.1469.

Workup

  1. customwas repeatedly evaporated in vacuo with CHCl3 in an attempt
  2. customto provide the N10-C11 imine form

Sources & evidence

ORD record
ord-77d118deb0ae44ddb336ad99b34cc489
Source dataset
uspto-grants-2007_09
Patent number
US07265105B2

Reaction notes

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