N-(tert-butoxycarbonyl)glycine → HCID 178472526, compound

HRID 1879574Notes

Reaction equation

HRID 1879574 reaction equation
[C:1]([O:5][C:6]([NH:8][CH2:9][C:10]([OH:12])=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1.Cl.[NH2:38][C@@:39]1([C:56]([O:58][CH2:59][CH3:60])=[O:57])[CH2:44][C@@H:43]([S:45][C:46]2[NH:50][CH:49]=[N:48][N:47]=2)[C@@H:42]2[C@H:40]1[C@H:41]2[C:51]([O:53][CH2:54][CH3:55])=[O:52].C(N(C(C)C)CC)(C)C>CN(C)C=O>[C:1]([O:5][C:6]([NH:8][CH2:9][C:10]([NH:38][C@@:39]1([C:56]([O:58][CH2:59][CH3:60])=[O:57])[CH2:44][C@@H:43]([S:45][C:46]2[NH:50][CH:49]=[N:48][N:47]=2)[C@@H:42]2[C@H:40]1[C@H:41]2[C:51]([O:53][CH2:54][CH3:55])=[O:52])=[O:12])=[O:7])([CH3:2])([CH3:3])[CH3:4]

Participants

6

Reactant 4

HCID 78288N-(tert-butoxycarbonyl)glycineHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 178472528HCID 178472528, compound

Product 1

HCID 178472526HCID 178472526, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Add thionyl chloride (2.5 mL, 34.32 mmol) to a stirred solution of ditert-butyl (1R,2S,4R,5R,6R)-2-(tert-butoxycarbonylamino)-4-(4H-1,2,4-triazol-3-ylsulfanyl)bicyclo[3.1.0]hexane-2,6-dicarboxylate (2.1 g, 4.23 mmol) in ethanol (40 mL) at 0-5° C. dropwise over 5 minutes with caution (exothermic reaction). Remove the cooling bath and heat the reaction mixture at reflux temperature for 16 hours. Evaporate the volatiles and dry the residue under high vacuum for 7 hours to obtain a colorless foam of diethyl (1R,2S,4R,5R,6R)-2-amino-4-(4H-1,2,4-triazol-3-ylsulfanyl)bicyclo[3.1.0]hexane-2,6-dicarboxylate hydrochloride. Add then 2-(tert-butoxycarbonylamino)acetic acid (0.89 g, 5.07 mmol) and O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (1.93 g, 5.07 mmol) to a solution of diethyl (1R,2S,4R,5R,6R)-2-amino-4-(4H-1,2,4-triazol-3-ylsulfanyl)bicyclo[3.1.0]hexane-2,6-dicarboxylate hydrochloride in anhydrous N,N-dimethylformamide (20 mL) at room temperature then add diisopropylethylamine (2 mL, 11.47 mmol) and stir the resulting yellow solution under nitrogen for 18 hours. Concentrate the solvent and partition the residue between ethyl acetate (40 mL) and a saturated solution of sodium hydrogen carbonate in water (40 mL). Stir the mixture for 20 minutes, separate the layers and extract the aqueous layer with more ethyl acetate (40 mL). Combine the organics layers, dry on sodium sulfate and concentrate to dryness. Purify the residue by flash chromatography eluting with ethyl acetate: iso-hexane (80:20 to 100:0) to give the title compound as a colorless solid (2.42 g, 4.86 mmol). MS (m/z): 498 (M+1), 520 (M+23).

Workup

  1. additionAdd
  2. concentrationConcentrate the solvent
  3. custompartition the residue between ethyl acetate (40 mL)
  4. customseparate the layers
  5. extractionextract the aqueous layer with more ethyl acetate (40 mL)
  6. customCombine the organics layers, dry on sodium sulfate
  7. concentrationconcentrate to dryness
  8. customPurify the residue by flash chromatography
  9. washeluting with ethyl acetate: iso-hexane (80:20 to 100:0)

Sources & evidence

ORD record
ord-25a88f0951354f2ba9f16cc1b95c51da
Source dataset
uspto-grants-2012_11
Patent number
US08318184B2

Reaction notes

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