(1R,2S)-methyl 1-((1R,2R,5R)-5-(tert-butyldiphenylsilyloxy)-2-(hex-5-enyl(methyl)carbamoyl)cyclohexanecarboxamido)-2-vinylcyclopropanecarboxylate → (1aR,3aR,5R,7aR,15aS,Z)-methyl 5-(tert-butyldiphenylsilyloxy)-9-methyl-3,8-dioxo-1a,2,3,3a,4,5,6,7,7a,8,9,10,11,12,13,15a-hexadecahydro-1H-benzo[c]cyclopropa[g][1,6]diazacyclotetradecine-1a-carboxylate

HRID 926008Notes

Reaction equation

HRID 926008 reaction equation
[Si:1]([O:18][C@H:19]1[CH2:24][C@@H:23]([C:25]([NH:27][C@:28]2([C:33]([O:35][CH3:36])=[O:34])[CH2:30][C@H:29]2C=C)=[O:26])[C@H:22]([C:37](=[O:46])[N:38]([CH2:40][CH2:41][CH2:42][CH2:43][CH:44]=[CH2:45])[CH3:39])[CH2:21][CH2:20]1)([C:14]([CH3:17])([CH3:16])[CH3:15])([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1>ClC(Cl)C>[Si:1]([O:18][C@@H:19]1[CH2:20][CH2:21][C@H:22]2[C:37](=[O:46])[N:38]([CH3:39])[CH2:40][CH2:41][CH2:42][CH2:43][CH:44]=[CH:45][C@@H:30]3[CH2:29][C@@:28]3([C:33]([O:35][CH3:36])=[O:34])[NH:27][C:25](=[O:26])[C@@H:23]2[CH2:24]1)([C:14]([CH3:17])([CH3:15])[CH3:16])([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

3

Reactant 1

HCID 67213840(1R,2S)-methyl 1-((1R,2R,5R)-5-(tert-butyldiphenylsilyloxy)-2-(hex-5-enyl(methyl)carbamoyl)cyclohexanecarboxamido)-2-vinylcyclopropanecarboxylate

Product 1

HCID 131735010(1aR,3aR,5R,7aR,15aS,Z)-methyl 5-(tert-butyldiphenylsilyloxy)-9-methyl-3,8-dioxo-1a,2,3,3a,4,5,6,7,7a,8,9,10,11,12,13,15a-hexadecahydro-1H-benzo[c]cyclopropa[g][1,6]diazacyclotetradecine-1a-carboxylateYield 81%

Reagents, catalysts & solvents 1

HCID 63651,1-DichloroethaneSolvent

Procedure

To a solution of compound 41 (0.74 mmol) in dichloroethane (700 mL), degassed for 45 min by bubbling nitrogen, was Zhan 1B (4%, 22 mg) at 80° C. under continuous degassing with nitrogen. After the reaction was refluxed for 1 hr, a second portion of Zhan 1B (22 mg) was added. After heating for 1.5 hr, the reaction mixture was cooled down to room temperature, poured onto a silica pad, and eluted with DCM. The crude material was purified by chromatography on silica gel (DCM/MeOH) to yield compound 42 as a brown solid in 81% yield. MS (ESI, EI+): m/z=617 (MH+).

Workup

  1. customby bubbling nitrogen
  2. customat 80° C.
  3. customunder continuous degassing with nitrogen
  4. temperatureAfter the reaction was refluxed for 1 hr
  5. additiona second portion of Zhan 1B (22 mg) was added
  6. temperatureAfter heating for 1.5 hr
  7. additionpoured onto a silica pad
  8. washeluted with DCM
  9. customThe crude material was purified by chromatography on silica gel (DCM/MeOH)

Sources & evidence

ORD record
ord-85492f55d318411c9930d25a09e4a4cf
Source dataset
uspto-grants-2016_03
Patent number
US09284307B2

Reaction notes

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