4-Methylmorpholine → tert-butyl ((2R,3R)-1-hydroxy-3-methoxybutan-2-yl)carbamate

HRID 1968890Notes

Reaction equation

HRID 1968890 reaction equation
[NH:1]([C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])[C@H:2]([C:7](O)=[O:8])[C@@H:3]([CH3:6])[O:4][CH3:5].CN1CCOCC1.ClC(OCC(C)C)=O.[BH4-].[Na+]>ClC(Cl)C.O>[C:13]([O:12][C:10](=[O:11])[NH:1][C@H:2]([CH2:7][OH:8])[C@H:3]([O:4][CH3:5])[CH3:6])([CH3:15])([CH3:14])[CH3:16]

Participants

7

Reactant 4

HCID 79724-MethylmorpholineHCID 62365Isobutyl chloroformateHCID 4311764Sodium borohydrideHCID 15460346(2S,3R)-2-{[(tert-butoxy)carbonyl]amino}-3-methoxybutanoic acid

Product 1

HCID 11816842tert-butyl ((2R,3R)-1-hydroxy-3-methoxybutan-2-yl)carbamateYield 103.6%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 63651,1-DichloroethaneSolvent

Procedure

To a cold solution (−15° C.) of BocThr(Me)OH (5.14 g, 22 mmol) in dichloroethane (22 mL) were successively added N-methyl morpholine (2.44 mL, 22 mmol) and isobutyl chloroformate (2.99 mL, 22 mmol). After one min, the precipitate was filtered and washed with dichloroethane (5×4 mL). The filtrate and washings were combined in a large three neck flask in an ice-salt bath. A solution of NaBH4 (1.26 g, 33 mmol) in H2O (11 mL) was added at once, proceeding a strong evolution of gas, followed by H2O (500 mL). The mixture was then extracted with EtOAc (5×150 mL). The combined EtOAc was dried (Na2SO4) and concentrated to give the titled compound (5 g). MS (MH+ 220).

Workup

  1. filtrationthe precipitate was filtered
  2. washwashed with dichloroethane (5×4 mL)
  3. customThe filtrate and washings were combined in a large three neck flask in an ice-salt bath
  4. extractionThe mixture was then extracted with EtOAc (5×150 mL)
  5. dry with materialThe combined EtOAc was dried (Na2SO4)
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-9ece6fafd7ff45a581063177c7130666
Source dataset
uspto-grants-2013_04
Patent number
US08426414B2

Reaction notes

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