Formaldehyde → HCID 69285461, compound

HRID 2225262Notes

Reaction equation

HRID 2225262 reaction equation
[NH2:1][C@H:2]1[CH2:7][C@@H:6]([CH2:8][CH2:9][C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])[C@@H:5]([NH:17][C:18](=[O:33])[CH2:19][NH:20][C:21](=[O:32])[C:22]2[CH:27]=[CH:26][CH:25]=[C:24]([C:28]([F:31])([F:30])[F:29])[CH:23]=2)[CH2:4][CH2:3]1.N[C@H:35]1[CH2:40][C@@H](CCC(O)=O)[C@@H](NC(=O)CNC(=O)C2C=CC=C(C(F)(F)F)C=2)C[CH2:36]1.[C:63](O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C=O>ClCCCl.C(O)(=O)C.CC(C)=O>[CH:35]([N:1]([CH3:63])[C@H:2]1[CH2:7][C@@H:6]([CH2:8][CH2:9][C:10]([O:12][C:13]([CH3:15])([CH3:14])[CH3:16])=[O:11])[C@@H:5]([NH:17][C:18](=[O:33])[CH2:19][NH:20][C:21](=[O:32])[C:22]2[CH:27]=[CH:26][CH:25]=[C:24]([C:28]([F:31])([F:30])[F:29])[CH:23]=2)[CH2:4][CH2:3]1)([CH3:40])[CH3:36]

Participants

8

Reactant 4

HCID 712Formaldehyde2×HCID 5049666Sodium triacetoxyborohydride2×HCID 69284640HCID 69284640, compoundHCID 69285719HCID 69285719, compound

Product 1

HCID 69285461HCID 69285461, compound

Reagents, catalysts & solvents 3

HCID 111,2-DichloroethaneSolventHCID 176Acetic AcidSolventHCID 180AcetoneSolvent

Procedure

The crude mixture of tert-butyl 3-((1R,2S,5R)-5-amino-2-(2-(3-(trifluoromethyl)benzamido)acetamido)cyclohexyl)propanoate and 3-((1R,2S,5R)-5-amino-2-(2-(3-(trifluoromethyl)benzamido)acetamido)cyclohexyl)propanoic acid prepared in Example 7a, Step 6 was dissolved in 1,2-dichloroethane (2 mL) and treated sequentially with acetone (32 μL), acetic acid (25 μL) and sodium triacetoxyborohydride (92 mg). The mixture was stirred at rt for 19.5 h, then was treated with aqueous formaldehyde (33 μL). After 1.5 h, additional aqueous formaldehyde (20 μL) and sodium triacetoxyborohydride (50 mg) were added and the mixture was stirred for an additional 2.5 h. The mixture was concentrated under vacuum and the residue was partitioned between saturated aqueous NaHCO3 and ethyl acetate. The aqueous phase was extracted twice with ethyl acetate and the combined organic phases were dried over Na2SO4 and concentrated under vacuum to provide the title product, tert-butyl 3-((1R,2S,5R)-5-(isopropyl(methyl)amino)-2-(2-(3-(trifluoromethyl)benzamido)acetamido)cyclohexyl)propanoate, as a glassy foam (45 mg). MS found: (M+H)+=528.4.

Workup

  1. waitAfter 1.5 h
  2. stirringthe mixture was stirred for an additional 2.5 h
  3. concentrationThe mixture was concentrated under vacuum
  4. customthe residue was partitioned between saturated aqueous NaHCO3 and ethyl acetate
  5. extractionThe aqueous phase was extracted twice with ethyl acetate
  6. dry with materialthe combined organic phases were dried over Na2SO4
  7. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-5bf51426424b4e89a8155cd7643cd337
Source dataset
uspto-grants-2008_05
Patent number
US07378409B2

Reaction notes

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