1-Hydroxybenzotriazole → tert-Butyl methylcarbamate

HRID 1668418Notes

Reaction equation

HRID 1668418 reaction equation
[C:1]([O:5][C:6]([N:8](C)[C@@H:9](CC)C(O)=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(N(C(C)C)CC)(C)C.C(NC([C@H]1N2C(=O)[C@@H](N)CCC(=O)N2CCC1)=O)CC1C=CC=CC=1.C1C=CC2N(O)N=NC=2C=1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C.CCOCC>[C:1]([O:5][C:6](=[O:7])[NH:8][CH3:9])([CH3:4])([CH3:3])[CH3:2]

Participants

8

Reactant 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 15689337(2S)-2-(((1,1-Dimethylethoxy)carbonyl)methylamino)butanoic acidHCID 57612839HCID 57612839, compound

Product 1

HCID 527635tert-Butyl methylcarbamateYield 267.3%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolvent2×

Procedure

To a solution of (S)-2-(tert-butoxycarbonyl-methyl-amino)-butyric acid (167 mg, 0.77 mmol) in DMF (5 mL) at room temperature, is added diisopropylethylamine (0.48 mL) slowly. After stirring at room temperature for 20 minutes, the solution is transferred to another flask contained (1S,9S)-9-amino-6,10-dioxo-octahydro-pyridazino[1,2-a][1,2]diazepine-1-carboxylic acid phenethyl-amide (240 mg, 0.70 mmol), and then a solution of HOBT (125 mg, 0.92 mmol) and HBTU (350 mg, 0.92 mmol) in DMF (5 mL) is added to the reaction mixture. After stirring for 1.5 hours, the reaction solution is diluted with ether (20 mL), and washed with water (2×10 mL). The combined organic layers is concentrated. The crude product is diluted with CH2Cl2 (10 mL) and dried over Na2SO4, and purified by chromatography (CH2Cl2/MeOH:97/3) to give (S)-1-((4S,7S)-6,10-dioxo-4-phenethylcarbamoyl-octahydro-pyridazino[1,2-a][1,2]diazepin-7-ylcarbamoyl)-propyl]-methyl-carbamic acid tert-butyl ester (270 mg, 71.3%) as pale solid. (NMR and MS data confirmed, U-3133-69).

Workup

  1. customthe solution is transferred to another flask
  2. stirringAfter stirring for 1.5 hours
  3. washwashed with water (2×10 mL)
  4. concentrationThe combined organic layers is concentrated
  5. additionThe crude product is diluted with CH2Cl2 (10 mL)
  6. dry with materialdried over Na2SO4
  7. custompurified by chromatography (CH2Cl2/MeOH:97/3)

Sources & evidence

ORD record
ord-d9dfa86695e641d4b0f9e75d3a448e99
Source dataset
uspto-grants-2011_08
Patent number
US07989441B2

Reaction notes

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