tert-butyl N-(2-oxoethyl)carbamate → HCID 57657410, compound

HRID 1920764Notes

Reaction equation

HRID 1920764 reaction equation
[NH2:1][C@@H:2]([CH2:11][CH:12]1[CH2:17][CH2:16][CH2:15][CH2:14][CH2:13]1)[C:3]([NH:5][C:6]1[S:7][CH:8]=[CH:9][N:10]=1)=[O:4].[C:18]([O:22][C:23](=[O:28])[NH:24][CH2:25][CH:26]=O)([CH3:21])([CH3:20])[CH3:19].[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>C(Cl)Cl.CCOC(C)=O>[C:18]([O:22][C:23](=[O:28])[NH:24][CH2:25][CH2:26][NH:1][C@H:2]([C:3](=[O:4])[NH:5][C:6]1[S:7][CH:8]=[CH:9][N:10]=1)[CH2:11][CH:12]1[CH2:17][CH2:16][CH2:15][CH2:14][CH2:13]1)([CH3:21])([CH3:20])[CH3:19]

Participants

6

Reactant 3

HCID 4247255tert-butyl N-(2-oxoethyl)carbamateHCID 5049666Sodium triacetoxyborohydride2×HCID 57657360HCID 57657360, compound

Product 1

HCID 57657410HCID 57657410, compoundYield 35%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
50 °C

Procedure

A solution of compound 12B (2.03 g, 8 mmol), (2-oxo-ethyl)-carbamic acid tert-butyl ester (1.27 g, 8 mmol) and NaBH(OAc)3 (1.70 g, 8 mmol) in DCM (30 ml) was maintained at ambient temperature overnight followed by the addition of NaBH(OAc)3 (3.39 g, 16 mmol). Reaction mixture was stirred at 50° C. for 3 hours, diluted with EtOAc (200 ml) and extracted with water (200 ml), 5% aq. bicarbonate (200 ml) and brine (200 ml). Organic layer was dried over anh. MgSO4 and evaporated in vacuum. Residue was dissolved in DMSO (5 ml) and subjected to HPLC purification. [Phenomenex Gemini C-18 column, 110 Å (30×100 mm); flow rate=45 ml/min; mobile phase A: 100% water, 0.1% TFA; mobile phase B: 100% ACN, 0.1% TFA; gradient elution from 25% B to 70% B in 70 min., detection 254 nm]. Fractions containing the desired product were combined and neutralized with 1 M NaOH. ACN was evaporated. Residual solution was extracted with EtOAc (2×100 ml). Organic layer was dried over anh. MgSO4 and evaporated in vacuum to provide target product (1.10 g, 35%) as light yellow oil. LC-MS [M+H] 397.2 (C19H32N4O3S+H, requires 397.56).

Workup

  1. customReaction mixture
  2. extractionextracted with water (200 ml), 5% aq. bicarbonate (200 ml) and brine (200 ml)
  3. dry with materialOrganic layer was dried over anh. MgSO4
  4. customevaporated in vacuum
  5. dissolutionResidue was dissolved in DMSO (5 ml)
  6. customsubjected to HPLC purification
  7. wash[Phenomenex Gemini C-18 column, 110 Å (30×100 mm); flow rate=45 ml/min; mobile phase A: 100% water, 0.1% TFA; mobile phase B: 100% ACN, 0.1% TFA; gradient elution from 25% B to 70% B in 70 min., detection 254 nm]
  8. additionFractions containing the desired product
  9. customACN was evaporated
  10. extractionResidual solution was extracted with EtOAc (2×100 ml)
  11. dry with materialOrganic layer was dried over anh. MgSO4
  12. customevaporated in vacuum

Sources & evidence

ORD record
ord-8eea155acd304e8b90e343b8a9d2b3da
Source dataset
uspto-grants-2012_05
Patent number
US08173645B2

Reaction notes

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