4-Methylmorpholine → HCID 131733559, compound

HRID 1747232Notes

Reaction equation

HRID 1747232 reaction equation
[C:1]([NH:8][C@@H:9]([C:18](O)=[O:19])[CH2:10][C:11]1[CH:16]=[CH:15][CH:14]=[C:13]([I:17])[CH:12]=1)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].CN1CCOCC1.ClC(OCC(C)C)=O.[BH4-].[Na+]>C1COCC1.CC(N(C)C)=O>[C:4]([O:3][C:1](=[O:2])[NH:8][C@@H:9]([CH2:18][OH:19])[CH2:10][C:11]1[CH:16]=[CH:15][CH:14]=[C:13]([I:17])[CH:12]=1)([CH3:5])([CH3:7])[CH3:6]

Participants

7

Reactant 4

HCID 79724-MethylmorpholineHCID 62365Isobutyl chloroformateHCID 4311764Sodium borohydrideHCID 46737391N-(tert-Butoxycarbonyl)-3-iodo-D-phenylalanine

Product 1

HCID 131733559HCID 131733559, compound

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 31374DimethylacetamideSolvent

Procedure

A solution of Boc-3-iodo-D-phenylalanine (6.32 g, 16.2 mmol) and 4-methyl-morpholine (1.87 ml, 17 mol) in THF (13 mL) was added dropwise to a −15° C. solution of isobutyl chloroformate (2.22 mL, 17 mmol) in THF (13 mL) and the resulting suspension was stirred for 1 h. The cold reaction mixture was filtered and the filter cake was rinsed with THF. The filtrate was added dropwise to a 0° C. solution of NaBH4 (0.92 g, 24.2 mmol) in dimethylacetamide (7 mL) and the resulting suspension was warmed to RT and stirred for 1 h. The reaction mixture was cooled back to 0° C. and quenched with 1M aq. citric acid. Additional water was added and the mixture was concentrated in vacuo. The remaining aqueous phase was acidified with 1M aq. HCl before being filtered. The filter cake was rinsed with water and dried under HV to give the title compound as an orange solid that was used further without purification. LC-MS A: tR=0.84 min; [M-Me]+=362.93.

Workup

  1. customThe cold reaction mixture
  2. filtrationwas filtered
  3. washthe filter cake was rinsed with THF
  4. stirringstirred for 1 h
  5. temperatureThe reaction mixture was cooled back to 0° C.
  6. customquenched with 1M aq. citric acid
  7. additionAdditional water was added
  8. concentrationthe mixture was concentrated in vacuo
  9. filtrationbefore being filtered
  10. washThe filter cake was rinsed with water
  11. customdried under HV

Sources & evidence

ORD record
ord-ec55187e56e14069b56276fd51674f50
Source dataset
uspto-grants-2015_10
Patent number
US09150566B2

Reaction notes

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