Sodium triacetoxyborohydride → methyl 3-(((2R,3S)-3-(tert-butoxycarbonylamino)-2-hydroxy-4-phenylbutylamino)methyl)-5-methoxybenzoate

HRID 2071182Notes

Reaction equation

HRID 2071182 reaction equation
[NH2:1][CH2:2][C@@H:3]([OH:20])[C@@H:4]([NH:12][C:13](=[O:19])[O:14][C:15]([CH3:18])([CH3:17])[CH3:16])[CH2:5][C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1.[CH:21]([C:23]1[CH:24]=[C:25]([CH:30]=[C:31]([O:33][CH3:34])[CH:32]=1)[C:26]([O:28][CH3:29])=[O:27])=O.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>C1COCC1.C(O)(=O)C.CCOC(C)=O>[C:15]([O:14][C:13]([NH:12][C@@H:4]([CH2:5][C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1)[C@H:3]([OH:20])[CH2:2][NH:1][CH2:21][C:23]1[CH:24]=[C:25]([CH:30]=[C:31]([O:33][CH3:34])[CH:32]=1)[C:26]([O:28][CH3:29])=[O:27])=[O:19])([CH3:17])([CH3:16])[CH3:18]

Participants

7

Reactant 3

HCID 5049666Sodium triacetoxyborohydrideHCID 10333883tert-butyl (2S,3R)-4-amino-3-hydroxy-1-phenylbutan-2-ylcarbamateHCID 11310067Methyl 3-formyl-5-methoxybenzoate

Product 1

HCID 59569953methyl 3-(((2R,3S)-3-(tert-butoxycarbonylamino)-2-hydroxy-4-phenylbutylamino)methyl)-5-methoxybenzoate

Reagents, catalysts & solvents 3

HCID 176Acetic AcidCatalystHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of tert-butyl (2S,3R)-4-amino-3-hydroxy-1-phenylbutan-2-ylcarbamate (300 mg, 1.07 mmol) in THF was added methyl 3-formyl-5-methoxybenzoate (294 mg, ˜80% purity, 1.07 mmol) and stirred for 30 min at room temperature, NaB(OAc)3H (453.7 mg, 2.14 mmol) was then added portionwise in 30 min, finally 5 drops of acetic acid was added and the resulting mixture was stirred at the same temperature overnight. The reaction mixture was diluted with EtOAc, and washed with saturated aqueous NaHCO3. The organic layer was separated and dried (MgSO4). Concentration in vacuo, followed purification with flash chromatography to give the desired product methyl 3-(((2R,3S)-3-(tert-butoxycarbonylamino)-2-hydroxy-4-phenylbutylamino)methyl)-5-methoxybenzoate as a white solid (390 mg, % yield). 1H NMR (CDCl3): d: 8.583 (s, 1H), 7.447 (s, 1H), 7.298-7.166 (m, 5H), 7.092 (s, 1H), 3.899 (s, 3H), 3.832 (s, 4H), 3.779 (s, 2H), 3.572 (m, 1H), 2.2.946 (m, 1H), 2.777 (m, 1H), 2.711 (m, 2H), 1.330 (s, 9H).

Workup

  1. stirringthe resulting mixture was stirred at the same temperature overnight
  2. washwashed with saturated aqueous NaHCO3
  3. customThe organic layer was separated
  4. dry with materialdried (MgSO4)
  5. concentrationConcentration in vacuo
  6. custompurification with flash chromatography

Sources & evidence

ORD record
ord-9499269b440f4333bb1a4970c571cf3d
Source dataset
uspto-grants-2012_10
Patent number
US08299267B2

Reaction notes

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