Methanol → HCID 86634302, compound

HRID 1446686Notes

Reaction equation

HRID 1446686 reaction equation
[C:1]([O:5][C:6]([NH:8][C:9]1[S:10][C:11]([C:17]2([CH3:20])[CH2:19][CH2:18]2)=[C:12]([C:14](O)=[O:15])[N:13]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(N(CC)CC)C.ClC(OCC(C)C)=O.[BH4-].[Na+].CO>C1COCC1>[C:1]([O:5][C:6](=[O:7])[NH:8][C:9]1[S:10][C:11]([C:17]2([CH3:20])[CH2:19][CH2:18]2)=[C:12]([CH2:14][OH:15])[N:13]=1)([CH3:4])([CH3:2])[CH3:3]

Participants

7

Reactant 5

HCID 887MethanolHCID 8471TriethylamineHCID 62365Isobutyl chloroformateHCID 4311764Sodium borohydrideHCID 86634301HCID 86634301, compound

Product 1

HCID 86634302HCID 86634302, compoundYield 58.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

Dissolve 2-tert-butoxycarbonylamino-5-(1-methyl-cyclopropyl)-thiazole-4-carboxylic acid (2 g, 6.7 mmol) in THF (100 mL) and cool to 0° C. under nitrogen. Add triethylamine (0.93 mL, 1 equiv.) followed by the dropwise addition of isobutyl chloroformate (0.87 mL, 1 equiv.). Stir 30 minutes at 0° C. then filter, washing with THF. Cool filtrate back to 0° C. then add sodium borohydride (0.76 g, 3 equiv.) in one sum followed by the dropwise addition of methanol (4.1 mL, 15 equiv.). After 45 minutes at 0° C. remove cooling bath and let warm to room temperature for 15 minutes. Quench reaction (cautiously) with 1 N HCl (aq), approximately 50 mL. Extract with DCM. Wash organics with aqueous saturated sodium chloride. Dry organics over MgSO4 then filter and concentrate. Purify on silica gel (2:1 Hexanes:Ethyl Acetate→1:1 Hexanes:Ethyl Acetate) to give a white solid (1.11 g, 58%). LCMS (ES), m/z 229 (M+1, product→t Butyl).

Workup

  1. filtrationthen filter
  2. washwashing with THF
  3. customAfter 45 minutes at 0° C. remove
  4. temperaturecooling bath
  5. temperaturelet warm to room temperature for 15 minutes
  6. customQuench
  7. customreaction (cautiously) with 1 N HCl (aq), approximately 50 mL
  8. extractionExtract with DCM
  9. filtrationDry organics over MgSO4 then filter
  10. concentrationconcentrate
  11. customPurify on silica gel (2:1 Hexanes:Ethyl Acetate→1:1 Hexanes:Ethyl Acetate)

Sources & evidence

ORD record
ord-4014ef9e6f95413c965c0a6c11f1f5c0
Source dataset
uspto-grants-2010_02
Patent number
US07666879B2

Reaction notes

Loading…