Water → Di-tert-butyl (4-{(3R,4S,5S)-3-[(tert-butoxycarbonyl)amino]-4-[(methoxycarbonyl)amino]-5-methylpiperidin-1-yl}pyridin-3-yl)imidodicarbonate

HRID 924520Notes

Reaction equation

HRID 924520 reaction equation
[NH2:1][C@H:2]1[C@@H:7]([CH3:8])[CH2:6][N:5]([C:9]2[CH:14]=[CH:13][N:12]=[CH:11][C:10]=2[N:15]([C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:4][C@H:3]1[NH:30][C:31]([O:33][C:34]([CH3:37])([CH3:36])[CH3:35])=[O:32].CCN(C(C)C)C(C)C.Cl[C:48]([O:50][CH3:51])=[O:49].C([O-])([O-])=O.[Na+].[Na+].O>C(Cl)Cl>[C:34]([O:33][C:31]([NH:30][C@H:3]1[C@@H:2]([NH:1][C:48]([O:50][CH3:51])=[O:49])[C@@H:7]([CH3:8])[CH2:6][N:5]([C:9]2[CH:14]=[CH:13][N:12]=[CH:11][C:10]=2[N:15]([C:23]([O:25][C:26]([CH3:27])([CH3:29])[CH3:28])=[O:24])[C:16]([O:18][C:19]([CH3:20])([CH3:21])[CH3:22])=[O:17])[CH2:4]1)=[O:32])([CH3:36])([CH3:35])[CH3:37]

Participants

7

Reactant 5

HCID 962WaterHCID 6586Methyl chloroformateHCID 10340Sodium CarbonateHCID 81531DiisopropylethylamineHCID 86726960di-tert-butyl (4-{(3R,4S,5S)-4-amino-3-[(tert-butoxycarbonyl)amino]-5-methylpiperidin-1-yl}pyridin-3-yl)imidodicarbonate

Product 1

HCID 86726959Di-tert-butyl (4-{(3R,4S,5S)-3-[(tert-butoxycarbonyl)amino]-4-[(methoxycarbonyl)amino]-5-methylpiperidin-1-yl}pyridin-3-yl)imidodicarbonateYield 109.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

To a solution of di-tert-butyl (4-{(3R,4S,5S)-4-amino-3-[(tert-butoxycarbonyl)amino]-5-methylpiperidin-1-yl}pyridin-3-yl)imidodicarbonate (1.27 g, 2.43 mmol) in DCM (50.0 mL) at 0° C., DIPEA (983 mg, 7.60 mmol) was added followed by a solution of methyl chloroformate (244 mg, 2.59 mmol) in DCM (10 mL). The solution was stirred at 0° C. for 30 min., then at room temperature for additional 30 min., then the reaction was quenched with 1.0 M aq. Na2CO3 in water (75.0 mL, 75.0 mmol). The organic layer was separated, washed with brine, then dried over Na2SO4, filtered and concentrated to give the crude sub-title compound as a yellow foamy solid (1.545 g, 109%). The crude product was used directly in the next step without further purification. LCMS calc. for C28H46N5O8 (M+H)+: m/z=580.3. Found: 580.3.

Workup

  1. waitat room temperature for additional 30 min.
  2. customThe organic layer was separated
  3. washwashed with brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-30104f0f01f940b4b85b03322e34d629
Source dataset
uspto-grants-2016_03
Patent number
US09278950B2

Reaction notes

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