Hydrochloric Acid → 3-(6-[N,N-bis(tert-butoxycarbonyl)amino]-5-methyl-pyridin-3-yl)-2-hydroxymethyl-2-methyl-propionic acid ethyl ester

HRID 1789821Notes

Reaction equation

HRID 1789821 reaction equation
ClC(OC)=O.[CH2:6]([O:8][C:9](=[O:38])[C:10]([CH2:15][C:16]1[CH:17]=[N:18][C:19]([N:23]([C:31]([O:33][C:34]([CH3:37])([CH3:36])[CH3:35])=[O:32])[C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])=[C:20]([CH3:22])[CH:21]=1)([CH3:14])[C:11](O)=[O:12])[CH3:7].CCN(CC)CC.[BH4-].[Na+].Cl>C1COCC1.C(Cl)Cl>[CH2:6]([O:8][C:9](=[O:38])[C:10]([CH2:11][OH:12])([CH3:14])[CH2:15][C:16]1[CH:17]=[N:18][C:19]([N:23]([C:31]([O:33][C:34]([CH3:37])([CH3:36])[CH3:35])=[O:32])[C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])=[C:20]([CH3:22])[CH:21]=1)[CH3:7]

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 6586Methyl chloroformateHCID 8471TriethylamineHCID 4311764Sodium borohydrideHCID 541480032-(6-[N,N-bis(tert-butoxycarbonyl)amino]-5-methyl-pyridin-3-ylmethyl)-2-methyl-malonic acid monoethyl ester

Product 1

HCID 542575253-(6-[N,N-bis(tert-butoxycarbonyl)amino]-5-methyl-pyridin-3-yl)-2-hydroxymethyl-2-methyl-propionic acid ethyl esterYield 49%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

Methyl chloroformate (338 μL, 4.4 mmol) was added dropwise to a solution of crude 2-(6-[N,N-bis(tert-butoxycarbonyl)amino]-5-methyl-pyridin-3-yl methyl)-2-methyl-malonic acid monoethyl ester (1.9 g) and Et3N (641 μL, 4.6 mmol) in THF (30 mL) at −20° C. The reaction mixture was stirred for 50 min., filtered and added dropwise to a suspension of NaBH4 (182 mg, 4.8 mmol) in THF (30 mL) at −20° C. The reaction was stirred for 16 h at room temperature. 0.5 M HCl was added followed by methylene chloride. The organic phase was washed with brine and dried. Concentration under reduced pressure followed by chromathography (toluene/EtOAc, 10:1→1:3) gave 3-(6-[N,N-bis(tert-butoxycarbonyl)-amino]-5-methyl-pyridin-3-yl)-2-hydroxymethyl-2-methyl-propionic acid ethyl ester (885 mg, 49%).

Workup

  1. filtrationfiltered
  2. stirringThe reaction was stirred for 16 h at room temperature
  3. washThe organic phase was washed with brine
  4. customdried
  5. concentrationConcentration under reduced pressure

Sources & evidence

ORD record
ord-b2cf4b90866342179f06cdfb89ca06a9
Source dataset
uspto-grants-2006_07
Patent number
US07071175B1

Reaction notes

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