Dimethylformamide → tert-butyl (6R,7R)-7-[[(2Z)-2-methoxyimino-2-[2-(tritylamino)-1,3-thiazol-4-yl]acetyl]amino]-3-(oxan-2-yl)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate

HRID 612281Notes

Reaction equation

HRID 612281 reaction equation
S(Cl)(C)(=O)=O.Cl.CO[CH:9]([C:13]1[N:14]=[C:15]([NH:19][C:20]([C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=2)([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[S:16](=N)[CH:17]=1)[C:10]([OH:12])=O.C([N:42](CC)C(C)C)(C)C.[NH2:48][C@@H:49]1[C:69](=[O:70])[N:51]2[C:52]([C:62]([O:64][C:65]([CH3:68])([CH3:67])[CH3:66])=[O:63])=[C:53]([CH:56]3[CH2:61][CH2:60][CH2:59][CH2:58][O:57]3)[CH2:54][S:55][C@H:50]12.CN([CH:74]=[O:75])C>N1C=CC=CC=1>[CH3:74][O:75]/[N:42]=[C:9](/[C:13]1[N:14]=[C:15]([NH:19][C:20]([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)([C:33]2[CH:34]=[CH:35][CH:36]=[CH:37][CH:38]=2)[C:21]2[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=2)[S:16][CH:17]=1)\[C:10]([NH:48][C@@H:49]1[C:69](=[O:70])[N:51]2[C:52]([C:62]([O:64][C:65]([CH3:67])([CH3:66])[CH3:68])=[O:63])=[C:53]([CH:56]3[CH2:61][CH2:60][CH2:59][CH2:58][O:57]3)[CH2:54][S:55][C@H:50]12)=[O:12]

Participants

7

Reactant 5

HCID 6228Dimethylformamide2×HCID 31297Methanesulfonyl chlorideHCID 81531DiisopropylethylamineHCID 53828043t-butyl (6R,7R)-7amino-3-(tetrahydropyran-2-yl)-ceph-3-em-4-carboxylateHCID 178478975HCID 178478975, compound

Product 1

HCID 141582271tert-butyl (6R,7R)-7-[[(2Z)-2-methoxyimino-2-[2-(tritylamino)-1,3-thiazol-4-yl]acetyl]amino]-3-(oxan-2-yl)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylateYield 62%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Conditions

Temperature
-50 °C

Procedure

Mesyl chloride (121 mg, 82 μl) was added to 2-(Z)-methoxy-imino-2-(2-tritylaminothiazol-4-yl)acetic acid hydrochloride (466 mg) and N,N-diisopropylethylamine (252 mg, 340 μl) in dry DMF (10 ml) at -50° C. under argon and stirred at -50° C. for 1 h. Then t-butyl (6R,7R)-7amino-3- (tetrahydropyran-2-yl)-ceph-3-em-4-carboxylate (Isomer A, 300 mg) in dry DMF (5 ml) followed by pyridine (70 mg, 72 μl) were added and reaction mixture left for a further 1 h whilst warming to ambient temperature. The reaction mixture was partitioned between ethyl acetate and water, reextracted with ethyl acetate, organic extracts washed with water (x3) and brine, dried, concentrated and flash chromatography (eluting with 30, 40, 50, 60% ethyl acetate in hexane) to afford the title compound as a pale yellow foam (420 mg, 62%); νmax (CH2Cl2) 3420, 1784, 1732 (shoulder), 1717, 1685 cm-1 ; δH (CDCl3), 1.53 (9 H, s) overlapping 1.4-1.7 (4 H, m), 1.73-1.94 (2 H, m), 3.38-3.58 (3 H, m), 3.95-4.00 (1 H, m), 4.07 (3 H, s), 4.54-4.59 (1 H, m), 5.02 (1 H, d, J4.8 Hz), 5.90 (1 H, dd, J4.5, 9.1 Hz) 6.74 (1 H, s), 6.86 (1 H, d, J8.8 Hz), 7.04 (1 H, s) and 7.30 (15 H, s). [Mass spectrum: +ve ion (3-nitrobenzyl alcohol, sodium acetate) MNa+ (788)].

Workup

  1. additionwere added
  2. customreaction mixture
  3. waitleft for a further 1 h
  4. temperaturewhilst warming to ambient temperature
  5. customThe reaction mixture was partitioned between ethyl acetate and water
  6. washwashed with water (x3) and brine
  7. customdried
  8. concentrationconcentrated
  9. washflash chromatography (eluting with 30, 40, 50, 60% ethyl acetate in hexane)

Sources & evidence

ORD record
ord-8bf52f8d39574935a3d4a403a78b4e30
Source dataset
uspto-grants-1999_12
Patent number
US06001997

Reaction notes

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