N-(tert-butoxycarbonyl)glycine → HCID 11854859, compound

HRID 2261462Notes

Reaction equation

HRID 2261462 reaction equation
[NH2:1][CH2:2][CH:3]([OH:30])[CH2:4][O:5][C:6]1[C:11]([CH3:12])=[CH:10][C:9]([CH2:13][CH2:14][C:15]([C:17]2[S:24][C:23]([CH3:25])=[C:22]3[C:18]=2[CH2:19][C@H:20]2[C:26]([CH3:28])([CH3:27])[C@H:21]23)=[O:16])=[CH:8][C:7]=1[CH3:29].CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.C(OC([NH:69][CH2:70][C:71](O)=[O:72])=O)(C)(C)C>C(Cl)Cl.CC(=O)OCC>[NH2:69][CH2:70][C:71]([NH:1][CH2:2][CH:3]([OH:30])[CH2:4][O:5][C:6]1[C:11]([CH3:12])=[CH:10][C:9]([CH2:13][CH2:14][C:15](=[O:16])[C:17]2[S:24][C:23]([CH3:25])=[C:22]3[C:18]=2[CH2:19][C@H:20]2[C:26]([CH3:27])([CH3:28])[C@H:21]23)=[CH:8][C:7]=1[CH3:29])=[O:72]

Participants

7

Reactant 4

HCID 78288N-(tert-butoxycarbonyl)glycineHCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 11853581HCID 11853581, compound

Product 1

HCID 11854859HCID 11854859, compoundYield 3.8%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of 3-[4-(3-amino-2-hydroxy-propoxy)-3,5-dimethyl-phenyl]-1-((1aS,5aR)-1,1,2-trimethyl-1,1a,5,5a-tetrahydro-3-thia-cyclopropa[a]pentalen-4-yl)-propan-1-one (70 mg, 0.164 mmol, Example 99) in DCM (3 mL) is treated with DIPEA (85 mg, 0.655 mmol), TBTU (74 mg, 0.23 mmol) and tert. butoxycarbonyl glycine (43 mg, 0.246 mmol) and the reaction mixture is stirred at rt for 1 h. The mixture is diluted with EA and washed with sat. aq. NaHCO3 and brine. The organic extract is dried over MgSO4, filtered and evaporated. The residue is dissolved in DCM (2 mL) and TFA (0.1 mL) is added. The mixture is stirred at rt for 3 h before another portion of TFA (0.02 mL) is added. Stirring is continued for 1 h. The mixture is diluted with EA, washed twice with a sat. aq. NaHCO3 solution, dried over MgSO4, filtered and evaporated. The crude product is purified by chromatography on prep. TLC plates with DCM:methanol 9:1 to give 2-amino-N-(3-{2,6-dimethyl-4-[3-oxo-3-((1aS,5aR)-1,1,2-trimethyl-1,1a,5,5a-tetrahydro-3-thia-cyclopropa[a]pentalen-4-yl)-propyl]-phenoxy}-2-hydroxy-propyl)-acetamide (3 mg) as a colourless resin; LC-MS: tR=0.86 min, [M+1]+=485.33.

Workup

  1. washwashed with sat. aq. NaHCO3 and brine
  2. extractionThe organic extract
  3. dry with materialis dried over MgSO4
  4. filtrationfiltered
  5. customevaporated
  6. dissolutionThe residue is dissolved in DCM (2 mL)
  7. additionTFA (0.1 mL) is added
  8. stirringThe mixture is stirred at rt for 3 h before another portion of TFA (0.02 mL)
  9. additionis added
  10. stirringStirring
  11. waitis continued for 1 h
  12. additionThe mixture is diluted with EA
  13. washwashed twice with a sat. aq. NaHCO3 solution
  14. dry with materialdried over MgSO4
  15. filtrationfiltered
  16. customevaporated
  17. customThe crude product is purified by chromatography on prep

Sources & evidence

ORD record
ord-c93cb102d1f64088ad4def4336d4d2fc
Source dataset
uspto-grants-2010_12
Patent number
US07846964B2

Reaction notes

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