L-Alanine → (3S)-4,4-dimethoxytetrahydro-2H-pyran-3-amine

HRID 407187Notes

Reaction equation

HRID 407187 reaction equation
[CH3:1][O:2][C:3]1([O:10][CH3:11])[CH2:8][CH2:7][O:6][CH2:5][C:4]1=O.P([O-])(O)(O)=O.[K+].C([O-])=O.[Na+].[NH2:22][C@H](C(O)=O)C.[OH-].[Na+].C1N=C(N)C2N=CN([C@@H]3O[C@H](COP(OP(OC[C@H]4O[C@@H](N5C=C(C(N)=O)CC=C5)[C@H](O)[C@@H]4O)(O)=O)(O)=O)[C@@H](O)[C@H]3O)C=2N=1.C(=O)([O-])[O-].[K+].[K+]>C1(C)C=CC=CC=1.C(#N)C>[CH3:1][O:2][C:3]1([O:10][CH3:11])[CH2:8][CH2:7][O:6][CH2:5][C@@H:4]1[NH2:22]

Participants

10

Reactant 7

HCID 5950L-AlanineHCID 11430Potassium CarbonateHCID 14798Sodium HydroxideHCID 439153NadhHCID 516951Monobasic potassium phosphateHCID 2723810Sodium FormateHCID 118486434,4-Dimethoxyoxan-3-one

Product 1

HCID 67153728(3S)-4,4-dimethoxytetrahydro-2H-pyran-3-amine

Reagents, catalysts & solvents 2

HCID 1140TolueneSolvent2×HCID 6342AcetonitrileSolvent

Conditions

Temperature
45 °C

Procedure

A solution of 4,4-dimethoxydihydro-2H-pyran-3(4H)-one (172 g, 1.07 mol, see Example 1) in 310 mL of toluene was stirred in toluene for 30 min, then extracted 3× with water (270 mL). To the aqueous solution was added potassium dihydrogenphosphate (14.1 g, 0.104 mol), sodium formate (55.1 g, 0.810 mol), and L-Alanine (72.2 g, 0.810 mol). The pH was adjusted to 7.8 with 5 N NaOH, and NAD (0.810 g), PLP (0.810 g), LDH (0.162 g), FDH (1.62 g), and Codexis TA P1G5 (4.05 g) were added. The mixture was heated to 45° C. for 12 h, then cooled to rt. Potassium carbonate (324 g, 2.34 mol) was added, and after 30 min, the mixture was diluted with acetonitrile (810 mL). After 30 min, the reaction was filtered through a pad of solka-floc. The filtrate was partitioned and the aqueous layer was extracted with additional acetonitrile (810 mL). The combined organic fractions were concentrated in vacuo to provide crude (3S)-4,4-dimethoxytetrahydro-2H-pyran-3-amine.

Workup

  1. extractionextracted 3× with water (270 mL)
  2. additionwere added
  3. temperaturecooled to rt
  4. waitAfter 30 min
  5. filtrationthe reaction was filtered through a pad of solka-floc
  6. customThe filtrate was partitioned
  7. extractionthe aqueous layer was extracted with additional acetonitrile (810 mL)
  8. concentrationThe combined organic fractions were concentrated in vacuo

Sources & evidence

ORD record
ord-331f6a1e31644706abc80d902c6f9202
Source dataset
uspto-grants-2014_06
Patent number
US08754220B2

Reaction notes

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